{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:21:27Z","timestamp":1790605287503,"version":"4.1.0"},"reference-count":74,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T00:00:00Z","timestamp":1668729600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T00:00:00Z","timestamp":1668729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000024","name":"CIHR","doi-asserted-by":"crossref","award":["PJT-155993"],"award-info":[{"award-number":["PJT-155993"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000024","name":"CIHR","doi-asserted-by":"crossref","award":["PJT 168927"],"award-info":[{"award-number":["PJT 168927"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"name":"CRCHUM Internal funds"},{"name":"Vanier Canada"},{"DOI":"10.13039\/501100000156","name":"Fonds de Recherche du Qu\u00e9bec - Sant\u00e9","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurobiol"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract\n<\/jats:title><jats:p>In Alzheimer disease (AD), Tau, an axonal microtubule-associated protein, becomes hyperphosphorylated, detaches from microtubules, accumulates, and self-aggregates in the somatodendritic (SD) compartment. The accumulation of hyperphosphorylated and aggregated Tau is also seen in other neurodegenerative diseases such as frontotemporal lobar degeneration (FTLD-Tau). Previous studies reported a link between filamin A (FLNA), an actin-binding protein found in the SD compartment, and Tau pathology. In the present study, we further explored this link. We confirmed the interaction of Tau with FLNA in neuroblastoma 2a (N2a) cells. This interaction was mediated by a domain located between the 157 and 383 amino acids (a.a.) of Tau. Our results also revealed that the overexpression of FLNA resulted in an intracellular accumulation of wild-type Tau and Tau mutants (P301L, V337M, and R406W) in N2a cells. Tau phosphorylation and cleavage by caspase-3 but not its aggregation were increased upon FLNA overexpression in N2a cells. In the parietal cortex of AD brain, insoluble FLNA was increased compared to control brain, but it did not correlate with Tau pathology. Interestingly, Tau binding to microtubules and F-actin was preserved upon FLNA overexpression in N2a cells. Lastly, our results revealed that FLNA also induced the accumulation of annexin A2, a Tau interacting partner involved in its axonal localization. Collectively, our data indicated that in Tauopathies, FLNA could contribute to Tau pathology by acting on Tau and annexin A2.<\/jats:p>","DOI":"10.1007\/s12035-022-03121-w","type":"journal-article","created":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T08:30:11Z","timestamp":1668760211000},"page":"1021-1039","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Direct and Indirect Effects of Filamin A on Tau Pathology in Neuronal Cells"],"prefix":"10.1007","volume":"60","author":[{"given":"St\u00e9phanie","family":"Levert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Pilliod","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9tienne","family":"Aumont","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Armanville","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyntia","family":"Tremblay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Calon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2678-0020","authenticated-orcid":false,"given":"Nicole","family":"Leclerc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,18]]},"reference":[{"key":"3121_CR1","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1146\/annurev.neuro.24.1.1121","volume":"24","author":"V Lee","year":"2001","unstructured":"Lee V, Goedert M, Trojanowski J (2001) Neurodegenerative tauopathies. Annu Rev Neurosci 24:1121\u20131159","journal-title":"Annu Rev Neurosci"},{"issue":"1","key":"3121_CR2","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s00401-007-0237-2","volume":"114","author":"NJ Cairns","year":"2007","unstructured":"Cairns NJ et al (2007) Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol 114(1):5\u201322","journal-title":"Acta Neuropathol"},{"issue":"1","key":"3121_CR3","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/nrneurol.2015.225","volume":"12","author":"K Iqbal","year":"2016","unstructured":"Iqbal K, Liu F, Gong CX (2016) Tau and neurodegenerative disease: the story so far. Nat Rev Neurol 12(1):15\u201327","journal-title":"Nat Rev Neurol"},{"issue":"3","key":"3121_CR4","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/0022-510X(70)90063-8","volume":"11","author":"BE Tomlinson","year":"1970","unstructured":"Tomlinson BE, Blessed G, Roth M (1970) Observations on the brains of demented old people. J Neurol Sci 11(3):205\u2013242","journal-title":"J Neurol Sci"},{"issue":"3","key":"3121_CR5","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1007\/BF00688184","volume":"74","author":"I Alafuzoff","year":"1987","unstructured":"Alafuzoff I et al (1987) Histopathological criteria for progressive dementia disorders: clinical-pathological correlation and classification by multivariate data analysis. Acta Neuropathol 74(3):209\u2013225","journal-title":"Acta Neuropathol"},{"issue":"4","key":"3121_CR6","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/BF00308809","volume":"82","author":"H Braak","year":"1991","unstructured":"Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82(4):239\u2013259","journal-title":"Acta Neuropathol"},{"key":"3121_CR7","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1212\/WNL.42.3.631","volume":"42","author":"P Arriagada","year":"1992","unstructured":"Arriagada P et al (1992) Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer\u2019s disease. Neurology 42:631\u2013639","journal-title":"Neurology"},{"key":"3121_CR8","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1001\/archneur.1995.00540250089017","volume":"52","author":"L Bierer","year":"1995","unstructured":"Bierer L et al (1995) Neocortical neurofibrillary tangles correlate with dementia severity in Alzheimer\u2019s disease. Arch Neurol 52:81\u201388","journal-title":"Arch Neurol"},{"issue":"Pt 5","key":"3121_CR9","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1093\/brain\/aww027","volume":"139","author":"R Ossenkoppele","year":"2016","unstructured":"Ossenkoppele R et al (2016) Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer\u2019s disease. Brain 139(Pt 5):1551\u20131567","journal-title":"Brain"},{"issue":"6","key":"3121_CR10","doi-asserted-by":"publisher","first-page":"1723","DOI":"10.1093\/brain\/awz090","volume":"142","author":"MJ Pontecorvo","year":"2019","unstructured":"Pontecorvo MJ et al (2019) A multicentre longitudinal study of flortaucipir (18F) in normal ageing, mild cognitive impairment and Alzheimer\u2019s disease dementia. Brain 142(6):1723\u20131735","journal-title":"Brain"},{"issue":"2","key":"3121_CR11","doi-asserted-by":"publisher","first-page":"160","DOI":"10.4161\/cam.5.2.14401","volume":"5","author":"F Nakamura","year":"2011","unstructured":"Nakamura F, Stossel TP, Hartwig JH (2011) The filamins: organizers of cell structure and function. Cell Adh Migr 5(2):160\u2013169","journal-title":"Cell Adh Migr"},{"issue":"1","key":"3121_CR12","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.str.2004.10.014","volume":"13","author":"R Pudas","year":"2005","unstructured":"Pudas R et al (2005) Structural basis for vertebrate filamin dimerization. Structure 13(1):111\u2013119","journal-title":"Structure"},{"issue":"2","key":"3121_CR13","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1038\/35052082","volume":"2","author":"TP Stossel","year":"2001","unstructured":"Stossel TP et al (2001) Filamins as integrators of cell mechanics and signalling. Nat Rev Mol Cell Biol 2(2):138\u2013145","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"2","key":"3121_CR14","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.tcb.2009.12.001","volume":"20","author":"AX Zhou","year":"2010","unstructured":"Zhou AX, Hartwig JH, Akyurek LM (2010) Filamins in cell signaling, transcription and organ development. Trends Cell Biol 20(2):113\u2013123","journal-title":"Trends Cell Biol"},{"key":"3121_CR15","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2021.145575","volume":"784","author":"J Zhou","year":"2021","unstructured":"Zhou J et al (2021) The function and pathogenic mechanism of filamin A. Gene 784:145575","journal-title":"Gene"},{"issue":"5","key":"3121_CR16","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1083\/jcb.200707073","volume":"179","author":"F Nakamura","year":"2007","unstructured":"Nakamura F et al (2007) Structural basis of filamin A functions. J Cell Biol 179(5):1011\u20131025","journal-title":"J Cell Biol"},{"issue":"2","key":"3121_CR17","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1042\/BJ20120361","volume":"446","author":"S Ruskamo","year":"2012","unstructured":"Ruskamo S et al (2012) The C-terminal rod 2 fragment of filamin A forms a compact structure that can be extended. Biochem J 446(2):261\u2013269","journal-title":"Biochem J"},{"issue":"5","key":"3121_CR18","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1016\/j.bpj.2011.07.028","volume":"101","author":"H Chen","year":"2011","unstructured":"Chen H et al (2011) Differential mechanical stability of filamin A rod segments. Biophys J 101(5):1231\u20131237","journal-title":"Biophys J"},{"issue":"12","key":"3121_CR19","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1038\/35046533","volume":"2","author":"JM Bellanger","year":"2000","unstructured":"Bellanger JM et al (2000) The Rac1- and RhoG-specific GEF domain of Trio targets filamin to remodel cytoskeletal actin. Nat Cell Biol 2(12):888\u2013892","journal-title":"Nat Cell Biol"},{"issue":"5","key":"3121_CR20","doi-asserted-by":"publisher","first-page":"2122","DOI":"10.1073\/pnas.96.5.2122","volume":"96","author":"Y Ohta","year":"1999","unstructured":"Ohta Y et al (1999) The small GTPase RalA targets filamin to induce filopodia. Proc Natl Acad Sci U S A 96(5):2122\u20132128","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"9","key":"3121_CR21","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1038\/ncb838","volume":"4","author":"RK Vadlamudi","year":"2002","unstructured":"Vadlamudi RK et al (2002) Filamin is essential in actin cytoskeletal assembly mediated by p21-activated kinase 1. Nat Cell Biol 4(9):681\u2013690","journal-title":"Nat Cell Biol"},{"issue":"2","key":"3121_CR22","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1172\/JCI30376","volume":"117","author":"WR Thelin","year":"2007","unstructured":"Thelin WR et al (2007) Direct interaction with filamins modulates the stability and plasma membrane expression of CFTR. J Clin Invest 117(2):364\u2013374","journal-title":"J Clin Invest"},{"issue":"7","key":"3121_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108050","volume":"32","author":"C Haenig","year":"2020","unstructured":"Haenig C et al (2020) Interactome mapping provides a network of neurodegenerative disease proteins and uncovers widespread protein aggregation in affected brains. Cell Rep 32(7):108050","journal-title":"Cell Rep"},{"issue":"1","key":"3121_CR24","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s40478-018-0524-2","volume":"6","author":"Q Zhang","year":"2018","unstructured":"Zhang Q et al (2018) Integrated proteomics and network analysis identifies protein hubs and network alterations in Alzheimer\u2019s disease. Acta Neuropathol Commun 6(1):19","journal-title":"Acta Neuropathol Commun"},{"issue":"4","key":"3121_CR25","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1111\/jnc.14603","volume":"151","author":"KW Li","year":"2019","unstructured":"Li KW, Ganz AB, Smit AB (2019) Proteomics of neurodegenerative diseases: analysis of human post-mortem brain. J Neurochem 151(4):435\u2013445","journal-title":"J Neurochem"},{"issue":"3","key":"3121_CR26","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1523\/JNEUROSCI.18-03-00914.1998","volume":"18","author":"W Zhang","year":"1998","unstructured":"Zhang W et al (1998) Interaction of presenilins with the filamin family of actin-binding proteins. J Neurosci 18(3):914\u2013922","journal-title":"J Neurosci"},{"issue":"1","key":"3121_CR27","doi-asserted-by":"publisher","first-page":"235","DOI":"10.3233\/JAD-2010-100585","volume":"22","author":"Q Lu","year":"2010","unstructured":"Lu Q et al (2010) Alzheimer\u2019s disease-linked presenilin mutation (PS1M146L) induces filamin expression and gamma-secretase independent redistribution. J Alzheimers Dis 22(1):235\u2013245","journal-title":"J Alzheimers Dis"},{"issue":"29","key":"3121_CR28","doi-asserted-by":"publisher","first-page":"9773","DOI":"10.1523\/JNEUROSCI.0354-12.2012","volume":"32","author":"HY Wang","year":"2012","unstructured":"Wang HY et al (2012) Reducing amyloid-related Alzheimer\u2019s disease pathogenesis by a small molecule targeting filamin A. J Neurosci 32(29):9773\u20139784","journal-title":"J Neurosci"},{"key":"3121_CR29","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.neurobiolaging.2017.03.016","volume":"55","author":"HY Wang","year":"2017","unstructured":"Wang HY et al (2017) PTI-125 binds and reverses an altered conformation of filamin A to reduce Alzheimer\u2019s disease pathogenesis. Neurobiol Aging 55:99\u2013114","journal-title":"Neurobiol Aging"},{"issue":"34","key":"3121_CR30","doi-asserted-by":"publisher","first-page":"31547","DOI":"10.1074\/jbc.M212532200","volume":"278","author":"HY Wang","year":"2003","unstructured":"Wang HY et al (2003) Alpha 7 nicotinic acetylcholine receptors mediate beta-amyloid peptide-induced Tau protein phosphorylation. J Biol Chem 278(34):31547\u201331553","journal-title":"J Biol Chem"},{"issue":"12","key":"3121_CR31","doi-asserted-by":"publisher","first-page":"263","DOI":"10.20517\/2347-8659.2017.50","volume":"4","author":"LH Burns","year":"2017","unstructured":"Burns LH, Wang HY (2017) Altered filamin A enables amyloid beta-induced Tau hyperphosphorylation and neuroinflammation in Alzheimer\u2019s disease. Neuroimmunol Neuroinflamm 4(12):263\u2013271","journal-title":"Neuroimmunol Neuroinflamm"},{"key":"3121_CR32","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.brainres.2010.05.007","volume":"1345","author":"S Feuillette","year":"2010","unstructured":"Feuillette S et al (2010) Filamin-A and myosin VI colocalize with fibrillary Tau protein in Alzheimer\u2019s disease and FTDP-17 brains. Brain Res 1345:182\u2013189","journal-title":"Brain Res"},{"issue":"5","key":"3121_CR33","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1111\/acel.12501","volume":"15","author":"S Ayyadevara","year":"2016","unstructured":"Ayyadevara S et al (2016) Proteins that mediate protein aggregation and cytotoxicity distinguish Alzheimer\u2019s hippocampus from normal controls. Aging Cell 15(5):924\u2013939","journal-title":"Aging Cell"},{"issue":"21","key":"3121_CR34","doi-asserted-by":"publisher","first-page":"eabm5029","DOI":"10.1126\/sciadv.abm5029","volume":"8","author":"K Tsujikawa","year":"2022","unstructured":"Tsujikawa K et al (2022) Actin-binding protein filamin-A drives Tau aggregation and contributes to progressive supranuclear palsy pathology. Sci Adv 8(21):eabm5029","journal-title":"Sci Adv"},{"issue":"3","key":"3121_CR35","doi-asserted-by":"publisher","first-page":"122","DOI":"10.14802\/jmd.15033","volume":"8","author":"SY Im","year":"2015","unstructured":"Im SY, Kim YE, Kim YJ (2015) Genetics of progressive supranuclear palsy. J Mov Disord 8(3):122\u2013129","journal-title":"J Mov Disord"},{"issue":"10","key":"3121_CR36","doi-asserted-by":"publisher","first-page":"3563","DOI":"10.1007\/s11010-021-04179-1","volume":"476","author":"L Cheng","year":"2021","unstructured":"Cheng L, Tong Q (2021) Interaction of FLNA and ANXA2 promotes gefitinib resistance by activating the Wnt pathway in non-small-cell lung cancer. Mol Cell Biochem 476(10):3563\u20133575","journal-title":"Mol Cell Biochem"},{"issue":"4","key":"3121_CR37","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1083\/jcb.201007161","volume":"192","author":"A Gauthier-Kemper","year":"2011","unstructured":"Gauthier-Kemper A et al (2011) The frontotemporal dementia mutation R406W blocks Tau\u2019s interaction with the membrane in an annexin A2-dependent manner. J Cell Biol 192(4):647\u2013661","journal-title":"J Cell Biol"},{"issue":"21","key":"3121_CR38","doi-asserted-by":"publisher","first-page":"8065","DOI":"10.1074\/jbc.RA117.000490","volume":"293","author":"A Gauthier-Kemper","year":"2018","unstructured":"Gauthier-Kemper A et al (2018) Annexins A2 and A6 interact with the extreme N terminus of Tau and thereby contribute to Tau\u2019s axonal localization. J Biol Chem 293(21):8065\u20138076","journal-title":"J Biol Chem"},{"issue":"s1","key":"3121_CR39","doi-asserted-by":"publisher","first-page":"S161","DOI":"10.3233\/JAD-179939","volume":"64","author":"DA Bennett","year":"2018","unstructured":"Bennett DA et al (2018) Religious orders study and rush memory and aging project. J Alzheimers Dis 64(s1):S161\u2013S189","journal-title":"J Alzheimers Dis"},{"issue":"5","key":"3121_CR40","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1111\/nan.12599","volume":"46","author":"P Bourassa","year":"2020","unstructured":"Bourassa P et al (2020) Brain mural cell loss in the parietal cortex in Alzheimer\u2019s disease correlates with cognitive decline and TDP-43 pathology. Neuropathol Appl Neurobiol 46(5):458\u2013477","journal-title":"Neuropathol Appl Neurobiol"},{"issue":"3","key":"3121_CR41","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1159\/000096129","volume":"27","author":"DA Bennett","year":"2006","unstructured":"Bennett DA et al (2006) Decision rules guiding the clinical diagnosis of Alzheimer\u2019s disease in two community-based cohort studies compared to standard practice in a clinic-based cohort study. Neuroepidemiology 27(3):169\u2013176","journal-title":"Neuroepidemiology"},{"issue":"12","key":"3121_CR42","doi-asserted-by":"publisher","first-page":"1837","DOI":"10.1212\/01.wnl.0000219668.47116.e6","volume":"66","author":"DA Bennett","year":"2006","unstructured":"Bennett DA et al (2006) Neuropathology of older persons without cognitive impairment from two community-based studies. Neurology 66(12):1837\u20131844","journal-title":"Neurology"},{"issue":"2","key":"3121_CR43","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1093\/jnen\/nlw109","volume":"76","author":"C Tremblay","year":"2017","unstructured":"Tremblay C et al (2017) Association of neuropathological markers in the parietal cortex with antemortem cognitive function in persons with mild cognitive impairment and Alzheimer disease. J Neuropathol Exp Neurol 76(2):70\u201388","journal-title":"J Neuropathol Exp Neurol"},{"issue":"1","key":"3121_CR44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00401-011-0910-3","volume":"123","author":"TJ Montine","year":"2012","unstructured":"Montine TJ et al (2012) National Institute on Aging-Alzheimer\u2019s Association guidelines for the neuropathologic assessment of Alzheimer\u2019s disease: a practical approach. Acta Neuropathol 123(1):1\u201311","journal-title":"Acta Neuropathol"},{"issue":"5","key":"3121_CR45","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0036873","volume":"7","author":"V Plouffe","year":"2012","unstructured":"Plouffe V et al (2012) Hyperphosphorylation and cleavage at D421 enhance Tau secretion. PLoS ONE 7(5):e36873","journal-title":"PLoS ONE"},{"issue":"1","key":"3121_CR46","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1111\/bpa.12883","volume":"31","author":"L Reimer","year":"2021","unstructured":"Reimer L et al (2021) PKR kinase directly regulates Tau expression and Alzheimer\u2019s disease-related Tau phosphorylation. Brain Pathol 31(1):103\u2013119","journal-title":"Brain Pathol"},{"issue":"Pt 4","key":"3121_CR47","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1242\/jcs.103.4.953","volume":"103","author":"R Takemura","year":"1992","unstructured":"Takemura R et al (1992) Increased microtubule stability and alpha tubulin acetylation in cells transfected with microtubule-associated proteins MAP1B, MAP2 or Tau. J Cell Sci 103(Pt 4):953\u2013964","journal-title":"J Cell Sci"},{"issue":"1","key":"3121_CR48","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/0014-5793(74)80404-7","volume":"46","author":"T Wieland","year":"1974","unstructured":"Wieland T, Govindan VM (1974) Phallotoxins bind to actins. FEBS Lett 46(1):351\u2013353","journal-title":"FEBS Lett"},{"issue":"3","key":"3121_CR49","doi-asserted-by":"publisher","first-page":"105","DOI":"10.3390\/biom9030105","volume":"9","author":"K Melkova","year":"2019","unstructured":"Melkova K et al (2019) Structure and functions of microtubule associated proteins Tau and MAP2c: similarities and differences. Biomolecules 9(3):105","journal-title":"Biomolecules"},{"issue":"1","key":"3121_CR50","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1111\/jnc.13228","volume":"135","author":"C Xie","year":"2015","unstructured":"Xie C et al (2015) Identification of key amino acids responsible for the distinct aggregation properties of microtubule-associated protein 2 and Tau. J Neurochem 135(1):19\u201326","journal-title":"J Neurochem"},{"issue":"1","key":"3121_CR51","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1186\/gb-2004-6-1-204","volume":"6","author":"L Dehmelt","year":"2005","unstructured":"Dehmelt L, Halpain S (2005) The MAP2\/Tau family of microtubule-associated proteins. Genome Biol 6(1):204","journal-title":"Genome Biol"},{"issue":"10","key":"3121_CR52","doi-asserted-by":"publisher","first-page":"3289","DOI":"10.1091\/mbc.11.10.3289","volume":"11","author":"W Antonin","year":"2000","unstructured":"Antonin W et al (2000) The R-SNARE endobrevin\/VAMP-8 mediates homotypic fusion of early endosomes and late endosomes. Mol Biol Cell 11(10):3289\u20133298","journal-title":"Mol Biol Cell"},{"issue":"1","key":"3121_CR53","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.neuron.2014.09.009","volume":"84","author":"L Zhang","year":"2014","unstructured":"Zhang L et al (2014) MEK-ERK1\/2-dependent FLNA overexpression promotes abnormal dendritic patterning in tuberous sclerosis independent of mTOR. Neuron 84(1):78\u201391","journal-title":"Neuron"},{"issue":"1","key":"3121_CR54","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/S0165-0173(00)00019-9","volume":"33","author":"L Bu\u00e9e","year":"2000","unstructured":"Bu\u00e9e L et al (2000) Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Brain Res Rev 33(1):95\u2013130","journal-title":"Brain Res Brain Res Rev"},{"issue":"4","key":"3121_CR55","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1083\/jcb.136.4.845","volume":"136","author":"C Cunningham","year":"1997","unstructured":"Cunningham C et al (1997) Microtubule-associated protein 2c reorganizes both microtubules and microfilaments into distinct cytological structures in an actin-binding protein-280-deficient melanoma cell line. J Cell Biol 136(4):845\u2013857","journal-title":"J Cell Biol"},{"issue":"9","key":"3121_CR56","doi-asserted-by":"publisher","first-page":"1816","DOI":"10.1038\/sj.emboj.7601078","volume":"25","author":"MJ Hayes","year":"2006","unstructured":"Hayes MJ et al (2006) Regulation of actin dynamics by annexin 2. EMBO J 25(9):1816\u20131826","journal-title":"EMBO J"},{"issue":"5042","key":"3121_CR57","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1126\/science.1549777","volume":"255","author":"CC Cunningham","year":"1992","unstructured":"Cunningham CC et al (1992) Actin-binding protein requirement for cortical stability and efficient locomotion. Science 255(5042):325\u2013327","journal-title":"Science"},{"issue":"7","key":"3121_CR58","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1038\/s41556-022-00938-4","volume":"24","author":"TD Williams","year":"2022","unstructured":"Williams TD et al (2022) Actin remodelling controls proteasome homeostasis upon stress. Nat Cell Biol 24(7):1077\u20131087","journal-title":"Nat Cell Biol"},{"issue":"12","key":"3121_CR59","doi-asserted-by":"publisher","first-page":"11140","DOI":"10.1074\/jbc.M412242200","volume":"280","author":"M Zhang","year":"2005","unstructured":"Zhang M, Breitwieser GE (2005) High affinity interaction with filamin A protects against calcium-sensing receptor degradation. J Biol Chem 280(12):11140\u201311146","journal-title":"J Biol Chem"},{"key":"3121_CR60","doi-asserted-by":"publisher","first-page":"122","DOI":"10.3389\/fneur.2013.00122","volume":"4","author":"AS Chesser","year":"2013","unstructured":"Chesser AS, Pritchard SM, Johnson GV (2013) Tau clearance mechanisms and their possible role in the pathogenesis of Alzheimer disease. Front Neurol 4:122","journal-title":"Front Neurol"},{"key":"3121_CR61","doi-asserted-by":"crossref","unstructured":"Vaz-Silva J et al (2018) Endolysosomal degradation of Tau and its role in glucocorticoid-driven hippocampal malfunction. EMBO J 37(20):e99084","DOI":"10.15252\/embj.201899084"},{"issue":"13","key":"3121_CR62","doi-asserted-by":"publisher","first-page":"2936","DOI":"10.1093\/hmg\/dds125","volume":"21","author":"C Cook","year":"2012","unstructured":"Cook C et al (2012) Loss of HDAC6, a novel CHIP substrate, alleviates abnormal Tau accumulation. Hum Mol Genet 21(13):2936\u20132945","journal-title":"Hum Mol Genet"},{"issue":"4","key":"3121_CR63","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1042\/BST20120071","volume":"40","author":"Y Wang","year":"2012","unstructured":"Wang Y, Mandelkow E (2012) Degradation of Tau protein by autophagy and proteasomal pathways. Biochem Soc Trans 40(4):644\u2013652","journal-title":"Biochem Soc Trans"},{"key":"3121_CR64","volume":"2011","author":"DP Hanger","year":"2011","unstructured":"Hanger DP, Noble W (2011) Functional implications of glycogen synthase kinase-3-mediated Tau phosphorylation. Int J Alzheimers Dis 2011:352805","journal-title":"Int J Alzheimers Dis"},{"key":"3121_CR65","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2020.610037","volume":"13","author":"SL Morris","year":"2020","unstructured":"Morris SL et al (2020) Defined Tau phosphospecies differentially inhibit fast axonal transport through activation of two independent signaling pathways. Front Mol Neurosci 13:610037","journal-title":"Front Mol Neurosci"},{"issue":"24","key":"3121_CR66","doi-asserted-by":"publisher","first-page":"14282","DOI":"10.1016\/S0021-9258(18)71675-X","volume":"264","author":"M Chen","year":"1989","unstructured":"Chen M, Stracher A (1989) In situ phosphorylation of platelet actin-binding protein by cAMP-dependent protein kinase stabilizes it against proteolysis by calpain. J Biol Chem 264(24):14282\u201314289","journal-title":"J Biol Chem"},{"issue":"2\u20133","key":"3121_CR67","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/S0167-4889(01)00072-6","volume":"1538","author":"A van der Flier","year":"2001","unstructured":"van der Flier A, Sonnenberg A (2001) Structural and functional aspects of filamins. Biochim Biophys Acta 1538(2\u20133):99\u2013117","journal-title":"Biochim Biophys Acta"},{"issue":"2","key":"3121_CR68","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.abb.2005.12.006","volume":"446","author":"E Garcia","year":"2006","unstructured":"Garcia E, Stracher A, Jay D (2006) Calcineurin dephosphorylates the C-terminal region of filamin in an important regulatory site: a possible mechanism for filamin mobilization and cell signaling. Arch Biochem Biophys 446(2):140\u2013150","journal-title":"Arch Biochem Biophys"},{"issue":"12","key":"3121_CR69","doi-asserted-by":"publisher","first-page":"3095","DOI":"10.1016\/j.bpj.2009.08.059","volume":"97","author":"HS Chen","year":"2009","unstructured":"Chen HS, Kolahi KS, Mofrad MR (2009) Phosphorylation facilitates the integrin binding of filamin under force. Biophys J 97(12):3095\u20133104","journal-title":"Biophys J"},{"issue":"5","key":"3121_CR70","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1093\/hmg\/ddm011","volume":"16","author":"O Blard","year":"2007","unstructured":"Blard O et al (2007) Cytoskeleton proteins are modulators of mutant Tau-induced neurodegeneration in Drosophila. Hum Mol Genet 16(5):555\u2013566","journal-title":"Hum Mol Genet"},{"issue":"3","key":"3121_CR71","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1093\/genetics\/165.3.1233","volume":"165","author":"JM Shulman","year":"2003","unstructured":"Shulman JM, Feany MB (2003) Genetic modifiers of tauopathy in Drosophila. Genetics 165(3):1233\u20131242","journal-title":"Genetics"},{"issue":"8","key":"3121_CR72","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1038\/s41591-020-0938-9","volume":"26","author":"S Dujardin","year":"2020","unstructured":"Dujardin S et al (2020) Tau molecular diversity contributes to clinical heterogeneity in Alzheimer\u2019s disease. Nat Med 26(8):1256\u20131263","journal-title":"Nat Med"},{"key":"3121_CR73","doi-asserted-by":"publisher","first-page":"138","DOI":"10.3389\/fnagi.2017.00138","volume":"9","author":"N Groh","year":"2017","unstructured":"Groh N et al (2017) Age-dependent protein aggregation initiates amyloid-beta aggregation. Front Aging Neurosci 9:138","journal-title":"Front Aging Neurosci"},{"issue":"21","key":"3121_CR74","doi-asserted-by":"publisher","first-page":"7124","DOI":"10.1523\/JNEUROSCI.3439-13.2014","volume":"34","author":"QL Ma","year":"2014","unstructured":"Ma QL et al (2014) Loss of MAP function leads to hippocampal synapse loss and deficits in the Morris Water Maze with aging. J Neurosci 34(21):7124\u20137136","journal-title":"J Neurosci"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-022-03121-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-022-03121-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-022-03121-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T06:39:23Z","timestamp":1674110363000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12035-022-03121-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,18]]},"references-count":74,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["3121"],"URL":"https:\/\/doi.org\/10.1007\/s12035-022-03121-w","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,18]]},"assertion":[{"value":"24 August 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 November 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 November 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the Institutional Review Board (IRB) at Rush University Medical Center in accordance with the Common Rule (45CFR46, December 13, 2001) and any other governing regulations or subparts.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}