{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T02:13:58Z","timestamp":1777083238730,"version":"3.51.4"},"reference-count":87,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T00:00:00Z","timestamp":1741564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["ZE994"],"award-info":[{"award-number":["ZE994"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease characterized by the degeneration of upper and lower motoneurons. The four most frequently mutated genes causing familial ALS (fALS) are C9orf72, FUS, SOD1, and TARDBP. Some of the related wild-type proteins comprise intrinsically disordered regions (IDRs) which favor their assembly in liquid droplets\u2014the biophysical mechanism behind the formation of physiological granules such as stress granules (SGs). SGs assemble and dissolve dependent on the cellular condition. However, it has been suggested that transition from reversible SGs to irreversible aggregates contributes to the toxic properties of ALS-related mutated proteins. Sequestration of additional proteins within these aggregates may then result in downstream toxicity. While the exact downstream mechanisms remain elusive, rare ALS-causing mutations in the actin binding protein profilin\u20091 suggest an involvement of the actin cytoskeleton. Here, we hypothesize that profilin isoforms become sequestered in aggregates of ALS-associated proteins which induce subsequent dysregulation of the actin cytoskeleton. Interestingly, localization of neuronal profilin\u20092 in SGs was more pronounced compared with the ubiquitously expressed profilin\u20091. Accordingly, FUS and C9orf72 aggregates prominently sequestered profilin\u20092 but not profilin\u20091. Moreover, we observed a distinct sequestration of profilin\u20092 and G-actin to C9orf72 aggregates in different cellular models. On the functional level, we identified dysregulated actin dynamics in cells with profilin\u20092-sequestering aggregates. In summary, our results suggest a more common involvement of profilins in ALS pathomechanisms than indicated from the rarely occurring profilin mutations.<\/jats:p>","DOI":"10.1093\/hmg\/ddaf020","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T19:36:26Z","timestamp":1741635386000},"page":"882-893","source":"Crossref","is-referenced-by-count":1,"title":["Aggregates associated with amyotrophic lateral sclerosis sequester the actin-binding protein profilin 2"],"prefix":"10.1093","volume":"34","author":[{"given":"Sabrina","family":"Kubinski","sequence":"first","affiliation":[{"name":"Hannover Medical School, Institute of Neuroanatomy and Cell Biology , Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover ,","place":["Germany"]},{"name":"Center for Systems Neuroscience (ZSN) , Buenteweg 2, 30559 Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Claus","sequence":"additional","affiliation":[{"name":"Hannover Medical School, Institute of Neuroanatomy and Cell Biology , Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"Sch\u00fcning","sequence":"additional","affiliation":[{"name":"Hannover Medical School, Institute of Neuroanatomy and Cell Biology , Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover ,","place":["Germany"]},{"name":"Center for Systems Neuroscience (ZSN) , Buenteweg 2, 30559 Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andre","family":"Zeug","sequence":"additional","affiliation":[{"name":"Hannover Medical School , Cellular Neurophysiology, Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norman","family":"Kalmbach","sequence":"additional","affiliation":[{"name":"Hannover Medical School, Department of Neurology , Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Selma","family":"Staege","sequence":"additional","affiliation":[{"name":"Center for Systems Neuroscience (ZSN) , Buenteweg 2, 30559 Hannover ,","place":["Germany"]},{"name":"Hannover Medical School, Department of Neurology , Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Gschwendtberger","sequence":"additional","affiliation":[{"name":"Center for Systems Neuroscience (ZSN) , Buenteweg 2, 30559 Hannover ,","place":["Germany"]},{"name":"Hannover Medical School, Department of Neurology , Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Petri","sequence":"additional","affiliation":[{"name":"Center for Systems Neuroscience (ZSN) , Buenteweg 2, 30559 Hannover ,","place":["Germany"]},{"name":"Hannover Medical School, Department of Neurology , Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Wegner","sequence":"additional","affiliation":[{"name":"Center for Systems Neuroscience (ZSN) , Buenteweg 2, 30559 Hannover ,","place":["Germany"]},{"name":"Hannover Medical School, Department of Neurology , Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3824-9445","authenticated-orcid":false,"given":"Peter","family":"Claus","sequence":"additional","affiliation":[{"name":"Hannover Medical School, Institute of Neuroanatomy and Cell Biology , Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover ,","place":["Germany"]},{"name":"Center for Systems Neuroscience (ZSN) , Buenteweg 2, 30559 Hannover ,","place":["Germany"]},{"name":"Hannover Medical School , Laboratory of Molecular Neurosciences, Department of Psychiatry, Social Psychiatry and Psychotherapy, Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1611-8906","authenticated-orcid":false,"given":"Niko","family":"Hensel","sequence":"additional","affiliation":[{"name":"Hannover Medical School, Institute of Neuroanatomy and Cell Biology , Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover ,","place":["Germany"]},{"name":"Department of Anatomy and Cell Biology, Martin Luther University Halle-Wittenberg, Faculty of Medicine , Gro\u00dfe Steinstra\u00dfe 52, 06108 Halle (Saale) ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,3,10]]},"reference":[{"key":"2025050702470435200_ref1","doi-asserted-by":"crossref","first-page":"263","DOI":"10.3389\/fnmol.2017.00263","article-title":"Autophagy dysregulation in ALS: when protein aggregates get out of hand","volume":"10","author":"Ramesh","year":"2017","journal-title":"Front Mol Neurosci"},{"key":"2025050702470435200_ref2","doi-asserted-by":"crossref","first-page":"17085","DOI":"10.1038\/nrdp.2017.85","article-title":"Amyotrophic lateral sclerosis","volume":"3","author":"Hardiman","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"2025050702470435200_ref3","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1111\/ene.14393","article-title":"Amyotrophic lateral sclerosis: a clinical review","volume":"27","author":"Masrori","year":"2020","journal-title":"Eur J Neurol"},{"key":"2025050702470435200_ref4","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/j.nmd.2020.11.009","article-title":"The 2021 version of the gene table of neuromuscular disorders (nuclear genome)","volume":"30","author":"Benarroch","year":"2020","journal-title":"Neuromuscul Disord"},{"key":"2025050702470435200_ref5","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s00401-012-1022-4","article-title":"The genetics and neuropathology of amyotrophic lateral sclerosis","volume":"124","author":"Al-Chalabi","year":"2012","journal-title":"Acta Neuropathol"},{"key":"2025050702470435200_ref6","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/1750-1326-8-28","article-title":"Genetics of amyotrophic lateral sclerosis: an update","volume":"8","author":"Chen","year":"2013","journal-title":"Mol Neurodegener"},{"key":"2025050702470435200_ref7","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.tig.2018.03.001","article-title":"ALS genes in the genomic era and their implications for FTD","volume":"34","author":"Nguyen","year":"2018","journal-title":"Trends Genet"},{"key":"2025050702470435200_ref8","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.3389\/fnins.2019.01310","article-title":"ALS genetics, mechanisms, and therapeutics: where are we now?","volume":"13","author":"Mejzini","year":"2019","journal-title":"Front Neurosci"},{"key":"2025050702470435200_ref9","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/362059a0","article-title":"Mutations in Cu\/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis","volume":"362","author":"Rosen","year":"1993","journal-title":"Nature"},{"key":"2025050702470435200_ref10","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1136\/jmedgenet-2016-104271","article-title":"Genetics insight into the amyotrophic lateral sclerosis\/frontotemporal dementia spectrum","volume":"54","author":"Ji","year":"2017","journal-title":"J Med Genet"},{"key":"2025050702470435200_ref11","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1242\/jcs.110.15.1741","article-title":"TLS (FUS) binds RNA in vivo and engages in nucleo-cytoplasmic shuttling","volume":"110","author":"Zinszner","year":"1997","journal-title":"J Cell Sci"},{"key":"2025050702470435200_ref12","doi-asserted-by":"crossref","first-page":"4696","DOI":"10.1073\/pnas.1818415116","article-title":"Motor neuron disease-associated loss of nuclear TDP-43 is linked to DNA double-strand break repair defects","volume":"116","author":"Mitra","year":"2019","journal-title":"Proc Natl Acad Sci USA"},{"key":"2025050702470435200_ref13","doi-asserted-by":"crossref","first-page":"2676","DOI":"10.1093\/hmg\/ddt117","article-title":"ALS mutant FUS disrupts nuclear localization and sequesters wild-type FUS within cytoplasmic stress granules","volume":"22","author":"Vance","year":"2013","journal-title":"Hum Mol Genet"},{"key":"2025050702470435200_ref14","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.neulet.2010.04.068","article-title":"Alterations in subcellular localization of TDP-43 immunoreactivity in the anterior horns in sporadic amyotrophic lateral sclerosis","volume":"478","author":"Sasaki","year":"2010","journal-title":"Neurosci Lett"},{"key":"2025050702470435200_ref15","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.neuron.2011.09.010","article-title":"A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD","volume":"72","author":"Renton","year":"2011","journal-title":"Neuron"},{"key":"2025050702470435200_ref16","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.neuron.2011.09.011","article-title":"Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS","volume":"72","author":"DeJesus-Hernandez","year":"2011","journal-title":"Neuron"},{"key":"2025050702470435200_ref17","doi-asserted-by":"crossref","first-page":"e5815","DOI":"10.7717\/peerj.5815","article-title":"C9orf72, a protein associated with amyotrophic lateral sclerosis (ALS) is a guanine nucleotide exchange factor","volume":"6","author":"Iyer","year":"2018","journal-title":"PeerJ"},{"key":"2025050702470435200_ref18","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1080\/21541248.2016.1240495","article-title":"C9orf72 plays a central role in Rab GTPase-dependent regulation of autophagy","volume":"9","author":"Webster","year":"2018","journal-title":"Small GTPases"},{"key":"2025050702470435200_ref19","doi-asserted-by":"crossref","first-page":"E4968","DOI":"10.1073\/pnas.1315438110","article-title":"RAN proteins and RNA foci from antisense transcripts in C9ORF72 ALS and frontotemporal dementia","volume":"110","author":"Zu","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"2025050702470435200_ref20","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3389\/fnmol.2017.00035","article-title":"The role of dipeptide repeats in C9ORF72-related ALS-FTD","volume":"10","author":"Freibaum","year":"2017","journal-title":"Front Mol Neurosci"},{"key":"2025050702470435200_ref21","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1007\/s00401-013-1189-3","article-title":"Bidirectional transcripts of the expanded C9orf72 hexanucleotide repeat are translated into aggregating dipeptide repeat proteins","volume":"126","author":"Mori","year":"2013","journal-title":"Acta Neuropathol"},{"key":"2025050702470435200_ref22","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/j.neuron.2014.12.010","article-title":"Antisense proline-arginine RAN dipeptides linked to C9ORF72-ALS\/FTD form toxic nuclear aggregates that initiate in vitro and in vivo neuronal death","volume":"84","author":"Wen","year":"2014","journal-title":"Neuron"},{"key":"2025050702470435200_ref23","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1126\/science.1256800","article-title":"C9orf72 repeat expansions cause neurodegeneration in drosophila through arginine-rich proteins","volume":"345","author":"Mizielinska","year":"2014","journal-title":"Science"},{"key":"2025050702470435200_ref24","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1007\/s00018-016-2416-6","article-title":"Intrinsic disorder in proteins involved in amyotrophic lateral sclerosis","volume":"74","author":"Santamaria","year":"2017","journal-title":"Cell Mol Life Sci"},{"key":"2025050702470435200_ref25","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/s12551-020-00680-x","article-title":"Biological phase separation: cell biology meets biophysics","volume":"12","author":"Yoshizawa","year":"2020","journal-title":"Biophys Rev"},{"key":"2025050702470435200_ref26","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1083\/jcb.200512082","article-title":"RNA granules","volume":"172","author":"Anderson","year":"2006","journal-title":"J Cell Biol"},{"key":"2025050702470435200_ref27","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.chom.2008.03.004","article-title":"P bodies, stress granules, and viral life cycles","volume":"3","author":"Beckham","year":"2008","journal-title":"Cell Host Microbe"},{"key":"2025050702470435200_ref28","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.molcel.2018.02.025","article-title":"Systematic characterization of stress-induced RNA granulation","volume":"70","author":"Namkoong","year":"2018","journal-title":"Mol Cell"},{"key":"2025050702470435200_ref29","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/S1097-2765(00)00108-8","article-title":"Regulated translation initiation controls stress-induced gene expression in mammalian cells","volume":"6","author":"Harding","year":"2000","journal-title":"Mol Cell"},{"key":"2025050702470435200_ref30","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1083\/jcb.151.6.1257","article-title":"Dynamic shuttling of TIA-1 accompanies the recruitment of mRNA to mammalian stress granules","volume":"151","author":"Kedersha","year":"2000","journal-title":"J Cell Biol"},{"key":"2025050702470435200_ref31","doi-asserted-by":"crossref","first-page":"4469","DOI":"10.1091\/mbc.e08-05-0499","article-title":"Translationally repressed mRNA transiently cycles through stress granules during stress","volume":"19","author":"Mollet","year":"2008","journal-title":"Mol Biol Cell"},{"key":"2025050702470435200_ref32","doi-asserted-by":"crossref","first-page":"609698","DOI":"10.3389\/fcell.2021.609698","article-title":"Dr. Jekyll and Mr. Hyde? Physiology and pathology of neuronal stress granules","volume":"9","author":"Jeon","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"2025050702470435200_ref33","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.cell.2016.10.002","article-title":"C9orf72 dipeptide repeats impair the assembly, dynamics, and function of membrane-less organelles","volume":"167","author":"Lee","year":"2016","journal-title":"Cell"},{"key":"2025050702470435200_ref34","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.molcel.2015.08.018","article-title":"Formation and maturation of phase-separated liquid droplets by RNA-binding proteins","volume":"60","author":"Lin","year":"2015","journal-title":"Mol Cell"},{"key":"2025050702470435200_ref35","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.cell.2015.09.015","article-title":"Phase separation by low complexity domains promotes stress granule assembly and drives pathological fibrillization","volume":"163","author":"Molliex","year":"2015","journal-title":"Cell"},{"key":"2025050702470435200_ref36","doi-asserted-by":"crossref","first-page":"8083","DOI":"10.1523\/JNEUROSCI.0543-14.2014","article-title":"Profilin 1 associates with stress granules and ALS-linked mutations alter stress granule dynamics","volume":"34","author":"Figley","year":"2014","journal-title":"J Neurosci"},{"key":"2025050702470435200_ref37","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.neuron.2015.10.030","article-title":"ALS\/FTD mutation-induced phase transition of FUS liquid droplets and reversible hydrogels into irreversible hydrogels impairs RNP granule function","volume":"88","author":"Murakami","year":"2015","journal-title":"Neuron"},{"key":"2025050702470435200_ref38","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.cell.2015.07.047","article-title":"A liquid-to-solid phase transition of the ALS protein FUS accelerated by disease mutation","volume":"162","author":"Patel","year":"2015","journal-title":"Cell"},{"key":"2025050702470435200_ref39","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/s41583-019-0222-5","article-title":"Stress granules and neurodegeneration","volume":"20","author":"Wolozin","year":"2019","journal-title":"Nat Rev Neurosci"},{"key":"2025050702470435200_ref40","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1002\/ana.21147","article-title":"Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations","volume":"61","author":"Mackenzie","year":"2007","journal-title":"Ann Neurol"},{"key":"2025050702470435200_ref41","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1126\/science.1134108","article-title":"Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis","volume":"314","author":"Neumann","year":"2006","journal-title":"Science"},{"key":"2025050702470435200_ref42","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1177\/1073858417705059","article-title":"The actin cytoskeleton in SMA and ALS: how does it contribute to Motoneuron degeneration?","volume":"24","author":"Hensel","year":"2018","journal-title":"Neuroscientist"},{"key":"2025050702470435200_ref43","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/0014-5793(93)80262-S","article-title":"Cloning and expression of a novel human profilin variant, profilin II","volume":"330","author":"Honor\u00e9","year":"1993","journal-title":"FEBS Lett"},{"key":"2025050702470435200_ref44","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1007\/s00018-016-2372-1","article-title":"Profilin1 biology and its mutation, actin(g) in disease","volume":"74","author":"Alkam","year":"2017","journal-title":"Cell Mol Life Sci"},{"key":"2025050702470435200_ref45","doi-asserted-by":"crossref","first-page":"4865","DOI":"10.1093\/hmg\/ddr425","article-title":"The spinal muscular atrophy disease protein SMN is linked to the rho-kinase pathway via profilin","volume":"20","author":"N\u00f6lle","year":"2011","journal-title":"Hum Mol Genet"},{"key":"2025050702470435200_ref46","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nature11280","article-title":"Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis","volume":"488","author":"Wu","year":"2012","journal-title":"Nature"},{"key":"2025050702470435200_ref47","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/aja.1001940306","article-title":"Neuroblastoma x spinal cord (NSC) hybrid cell lines resemble developing motor neurons","volume":"194","author":"Cashman","year":"1992","journal-title":"Dev Dyn"},{"key":"2025050702470435200_ref48","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1007\/PL00000854","article-title":"HuR and mRNA stability","volume":"58","author":"Brennan","year":"2001","journal-title":"Cell Mol Life Sci"},{"key":"2025050702470435200_ref49","doi-asserted-by":"crossref","DOI":"10.3390\/genes14091790","article-title":"Identification and validation of reference genes for RT-qPCR analysis in reed canary grass during abiotic stress","volume":"14","author":"Jia","year":"2023","journal-title":"Genes (Basel)"},{"key":"2025050702470435200_ref50","doi-asserted-by":"crossref","first-page":"148089","DOI":"10.1016\/j.gene.2023.148089","article-title":"From stability to reliability: unveiling the un-biased reference genes in porcine ovarian granulosa cells under different conditions","volume":"897","author":"Huo","year":"2024","journal-title":"Gene"},{"key":"2025050702470435200_ref51","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s11910-018-0914-7","article-title":"Relation between stress granules and cytoplasmic protein aggregates linked to neurodegenerative diseases","volume":"18","author":"Dobra","year":"2018","journal-title":"Curr Neurol Neurosci Rep"},{"key":"2025050702470435200_ref52","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1007\/s12551-020-00723-3","article-title":"Profilin: many facets of a small protein","volume":"12","author":"Davey","year":"2020","journal-title":"Biophys Rev"},{"key":"2025050702470435200_ref53","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s12551-009-0010-y","article-title":"Structure and functions of profilins","volume":"1","author":"Krishnan","year":"2009","journal-title":"Biophys Rev"},{"key":"2025050702470435200_ref54","doi-asserted-by":"crossref","first-page":"3832","DOI":"10.1073\/pnas.051515498","article-title":"Profilin I is essential for cell survival and cell division in early mouse development","volume":"98","author":"Witke","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"2025050702470435200_ref55","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0378-1119(01)00855-1","article-title":"Genomic organization of profilin-III and evidence for a transcript expressed exclusively in testis","volume":"283","author":"Braun","year":"2002","journal-title":"Gene"},{"key":"2025050702470435200_ref56","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1093\/molehr\/gah132","article-title":"Novel testis-expressed profilin IV associated with acrosome biogenesis and spermatid elongation","volume":"11","author":"Obermann","year":"2005","journal-title":"Mol Hum Reprod"},{"key":"2025050702470435200_ref57","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1471-2091-3-12","article-title":"Mutational analysis of human profilin I reveals a second PI(4,5)-P2 binding site neighbouring the poly(L-proline) binding site","volume":"3","author":"Lambrechts","year":"2002","journal-title":"BMC Biochem"},{"key":"2025050702470435200_ref58","doi-asserted-by":"crossref","first-page":"8636","DOI":"10.1073\/pnas.91.18.8636","article-title":"X-ray structures of isoforms of the actin-binding protein profilin that differ in their affinity for phosphatidylinositol phosphates","volume":"91","author":"Fedorov","year":"1994","journal-title":"Proc Natl Acad Sci USA"},{"key":"2025050702470435200_ref59","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1006\/jmbi.1994.1461","article-title":"Crystallization and structure determination of bovine profilin at 2.0 a resolution","volume":"240","author":"Cedergren-Zeppezauer","year":"1994","journal-title":"J Mol Biol"},{"key":"2025050702470435200_ref60","doi-asserted-by":"crossref","first-page":"4620","DOI":"10.1016\/S0021-9258(17)41821-7","article-title":"Identification of the poly-L-proline-binding site on human profilin","volume":"269","author":"Metzler","year":"1994","journal-title":"J Biol Chem"},{"key":"2025050702470435200_ref61","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/bs.ircmb.2020.05.005","article-title":"Profilin choreographs actin and microtubules in cells and cancer","volume":"355","author":"Pimm","year":"2020","journal-title":"Int Rev Cell Mol Biol"},{"key":"2025050702470435200_ref62","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/0022-2836(77)90166-8","article-title":"Actin polymerizability is influenced by profilin, a low molecular weight protein in non-muscle cells","volume":"115","author":"Carlsson","year":"1977","journal-title":"J Mol Biol"},{"key":"2025050702470435200_ref63","doi-asserted-by":"crossref","first-page":"4597","DOI":"10.1038\/sj.emboj.7601874","article-title":"Structural basis for the recruitment of profilin-actin complexes during filament elongation by Ena\/VASP","volume":"26","author":"Ferron","year":"2007","journal-title":"EMBO J"},{"key":"2025050702470435200_ref64","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1091\/mbc.3.9.1015","article-title":"The control of actin nucleotide exchange by thymosin beta 4 and profilin. A potential regulatory mechanism for actin polymerization in cells","volume":"3","author":"Goldschmidt-Clermont","year":"1992","journal-title":"Mol Biol Cell"},{"key":"2025050702470435200_ref65","doi-asserted-by":"crossref","first-page":"1602.e17","DOI":"10.1016\/j.neurobiolaging.2014.10.032","article-title":"Novel mutations support a role for profilin 1 in the pathogenesis of ALS","volume":"36","author":"Smith","year":"2015","journal-title":"Neurobiol Aging"},{"key":"2025050702470435200_ref66","doi-asserted-by":"crossref","first-page":"1708.e1","DOI":"10.1016\/j.neurobiolaging.2012.10.009","article-title":"A novel phosphorylation site mutation in profilin 1 revealed in a large screen of US, Nordic, and German amyotrophic lateral sclerosis\/frontotemporal dementia cohorts","volume":"34","author":"Ingre","year":"2013","journal-title":"Neurobiol Aging"},{"key":"2025050702470435200_ref67","doi-asserted-by":"crossref","first-page":"1922.e1","DOI":"10.1016\/j.neurobiolaging.2013.01.013","article-title":"PFN1 mutations are rare in Han Chinese populations with amyotrophic lateral sclerosis","volume":"34","author":"Chen","year":"2013","journal-title":"Neurobiol Aging"},{"key":"2025050702470435200_ref68","doi-asserted-by":"crossref","first-page":"231","DOI":"10.3389\/fnmol.2019.00231","article-title":"Developmental expression of mutant PFN1 in motor neurons impacts neuronal growth and motor performance of young and adult mice","volume":"12","author":"Brettle","year":"2019","journal-title":"Front Mol Neurosci"},{"key":"2025050702470435200_ref69","doi-asserted-by":"crossref","first-page":"E6209","DOI":"10.1073\/pnas.1605964113","article-title":"Mutant PFN1 causes ALS phenotypes and progressive motor neuron degeneration in mice by a gain of toxicity","volume":"113","author":"Yang","year":"2016","journal-title":"Proc Natl Acad Sci USA"},{"key":"2025050702470435200_ref70","first-page":"686","article-title":"Mutant Profilin1 transgenic mice recapitulate cardinal features of motor neuron disease","volume":"26","author":"Fil","year":"2017","journal-title":"Hum Mol Genet"},{"key":"2025050702470435200_ref71","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1038\/ncb2580","article-title":"Stimulus-dependent phosphorylation of profilin-1 in angiogenesis","volume":"14","author":"Fan","year":"2012","journal-title":"Nat Cell Biol"},{"key":"2025050702470435200_ref72","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1096\/fj.201901883R","article-title":"Profilin2a-phosphorylation as a regulatory mechanism for actin dynamics","volume":"34","author":"Walter","year":"2020","journal-title":"FASEB J"},{"key":"2025050702470435200_ref73","doi-asserted-by":"crossref","first-page":"37908","DOI":"10.1074\/jbc.274.53.37908","article-title":"A role for polyproline motifs in the spinal muscular atrophy protein SMN. Profilins bind to and colocalize with smn in nuclear gems","volume":"274","author":"Giesemann","year":"1999","journal-title":"J Biol Chem"},{"key":"2025050702470435200_ref74","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/0092-8674(94)90199-6","article-title":"Dictyostelium amoebae that lack G-actin-sequestering profilins show defects in F-actin content, cytokinesis, and development","volume":"79","author":"Haugwitz","year":"1994","journal-title":"Cell"},{"key":"2025050702470435200_ref75","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.1038\/sj.emboj.7601737","article-title":"Profilin2 contributes to synaptic vesicle exocytosis, neuronal excitability, and novelty-seeking behavior","volume":"26","author":"Pilo Boyl","year":"2007","journal-title":"EMBO J"},{"key":"2025050702470435200_ref76","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.molcel.2017.02.013","article-title":"Phase separation of C9orf72 dipeptide repeats perturbs stress granule dynamics","volume":"65","author":"Boeynaems","year":"2017","journal-title":"Mol Cell"},{"key":"2025050702470435200_ref77","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1523\/JNEUROSCI.4988-09.2010","article-title":"Cytoplasmic mislocalization of TDP-43 is toxic to neurons and enhanced by a mutation associated with familial amyotrophic lateral sclerosis","volume":"30","author":"Barmada","year":"2010","journal-title":"J Neurosci"},{"key":"2025050702470435200_ref78","doi-asserted-by":"crossref","first-page":"e202000927","DOI":"10.26508\/lsa.202000927","article-title":"Comparative profiling of stress granule clearance reveals differential contributions of the ubiquitin system","volume":"4","author":"Tolay","year":"2021","journal-title":"Life Sci Alliance"},{"key":"2025050702470435200_ref79","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.tcb.2004.07.003","article-title":"The role of profilin complexes in cell motility and other cellular processes","volume":"14","author":"Witke","year":"2004","journal-title":"Trends Cell Biol"},{"key":"2025050702470435200_ref80","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1007\/s10571-020-00984-2","article-title":"A progressive loss of phosphoSer138-profilin aligns with symptomatic course in the R6\/2 mouse model of Huntington's disease: possible sex-dependent Signaling","volume":"42","author":"Baharani","year":"2020","journal-title":"Cell Mol Neurobiol"},{"key":"2025050702470435200_ref81","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.nbd.2008.02.007","article-title":"Expression of expanded polyglutamine targets profilin for degradation and alters actin dynamics","volume":"30","author":"Burnett","year":"2008","journal-title":"Neurobiol Dis"},{"key":"2025050702470435200_ref82","doi-asserted-by":"crossref","first-page":"1779.e5","DOI":"10.1016\/j.neurobiolaging.2014.01.016","article-title":"Reduced C9orf72 protein levels in frontal cortex of amyotrophic lateral sclerosis and frontotemporal degeneration brain with the C9ORF72 hexanucleotide repeat expansion","volume":"35","author":"Waite","year":"2014","journal-title":"Neurobiol Aging"},{"key":"2025050702470435200_ref83","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1038\/nn.4407","article-title":"C9ORF72 interaction with cofilin modulates actin dynamics in motor neurons","volume":"19","author":"Sivadasan","year":"2016","journal-title":"Nat Neurosci"},{"key":"2025050702470435200_ref84","doi-asserted-by":"crossref","first-page":"4070","DOI":"10.1523\/JNEUROSCI.0346-04.2004","article-title":"A syntaxin 1, Galpha(o), and N-type calcium channel complex at a presynaptic nerve terminal: analysis by quantitative immunocolocalization","volume":"24","author":"Li","year":"2004","journal-title":"J Neurosci"},{"key":"2025050702470435200_ref85","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/s42003-020-0791-x","article-title":"Serotonin 5-HT(4) receptor boosts functional maturation of dendritic spines via RhoA-dependent control of F-actin","volume":"3","author":"Schill","year":"2020","journal-title":"Commun Biol"},{"key":"2025050702470435200_ref86","first-page":"110","article-title":"Sequence data analysis for long disordered regions prediction in the Calcineurin family","volume":"8","author":"Romero","year":"1997","journal-title":"Genome Inf Ser Workshop Genome Inf"},{"key":"2025050702470435200_ref87","first-page":"30","article-title":"Predicting protein disorder for N-, C-, and internal regions","volume":"10","author":"Li","year":"1999","journal-title":"Genome Inf Ser Workshop Genome Inf"}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/34\/10\/882\/62369645\/ddaf020.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/34\/10\/882\/62369645\/ddaf020.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T06:47:21Z","timestamp":1746600441000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/34\/10\/882\/8068939"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,10]]},"references-count":87,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,3,10]]},"published-print":{"date-parts":[[2025,5,6]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddaf020","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,5,15]]},"published":{"date-parts":[[2025,3,10]]}}}