{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T13:27:32Z","timestamp":1758806852138,"version":"3.41.2"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"content-version":"vor","delay-in-days":4,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Biogen and Boehringer Ingelheim via the Psychiatry Consortium of the Medicines Discovery Catapult"},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Oxford Health Biomedical Research Centre"},{"name":"NIHR Oxford Health Biomedical Research Centre","award":["NIHR203316"],"award-info":[{"award-number":["NIHR203316"]}]},{"name":"UKRI BBSRC","award":["BB\/CCG1720\/1","BS\/E\/T\/000PR981","BBS\/E\/ER\/230001A","BBS\/E\/ER\/230001C"],"award-info":[{"award-number":["BB\/CCG1720\/1","BS\/E\/T\/000PR981","BBS\/E\/ER\/230001A","BBS\/E\/ER\/230001C"]}]},{"DOI":"10.13039\/501100002283","name":"Alzheimer\u2019s Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002283","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Kalirin is a multidomain protein with important roles in neurite outgrowth, and synaptic spine formation and remodeling. Genetic and pathophysiological links with various neuropsychiatric disorders associated with synaptic dysfunction and cognitive impairment have sparked interest in its potential as a pharmacological target. Multiple Kalirin proteoforms are detected in the adult human brain, yet we know little about the diversity of the transcripts that encode them or their tissue profiles. Here, we characterized full-length KALRN transcripts expressed in the adult human frontal lobe and hippocampus using rapid amplification of complementary DNA (cDNA) ends and nanopore long-read sequencing. For comparison with non-neural tissue, we also analyzed KALRN transcripts in the aorta. Multiple novel isoforms were identified and were largely similar between the two brain regions analyzed. Alternative splicing in the brain results in preferential inclusion of exon 37, which encodes 32 amino acids upstream of the second guanine nucleotide exchange factor (GEF) domain. Structural modeling predicts that a subset of these amino acids forms a conserved alpha helix. Although deletion of these amino acids had little effect on GEF activity, it did alter Kalirin-induced neurite outgrowth suggesting that this brain-enriched splicing event may be important for neural function. These data indicate that alternative splicing is potentially important for regulating Kalirin actions in the human brain.<\/jats:p>","DOI":"10.1093\/cercor\/bhae470","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T19:56:57Z","timestamp":1733860617000},"source":"Crossref","is-referenced-by-count":1,"title":["Identification and characterization of human <i>KALRN<\/i> mRNA and Kalirin protein isoforms"],"prefix":"10.1093","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2004-4348","authenticated-orcid":false,"given":"Arne W","family":"Mould","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of Oxford , Warneford Hospital, Oxford OX3 7JX ,","place":["United Kingdom"]},{"name":"Oxford Health NHS Foundation Trust , Warneford Hospital, Oxford OX3 7JX,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J","family":"Wright","sequence":"additional","affiliation":[{"name":"Earlham Institute , Norwich Research Park, Norwich NR4 7UZ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus D","family":"Bornemann","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co. KG , 65 Birkendorfer Stra\u00dfe, 88397, Biberach an der Ri\u00df ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bastian","family":"Hengerer","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co. KG , 65 Birkendorfer Stra\u00dfe, 88397, Biberach an der Ri\u00df ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rob","family":"Pinnock","sequence":"additional","affiliation":[{"name":"Biogen Idec Ltd , 5 Roxborough Way, Maidenhead SL6 3UD,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward","family":"Drydale","sequence":"additional","affiliation":[{"name":"Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford , Roosevelt Drive, Oxford OX3 7BN,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Bancroft","sequence":"additional","affiliation":[{"name":"Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford , Roosevelt Drive, Oxford OX3 7BN,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola A L","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Oxford , Warneford Hospital, Oxford OX3 7JX ,","place":["United Kingdom"]},{"name":"Oxford Health NHS Foundation Trust , Warneford Hospital, Oxford OX3 7JX,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annette","family":"von Delft","sequence":"additional","affiliation":[{"name":"Centre for Medicines Discovery, NDM Research Building, University of Oxford , Roosevelt Drive, Oxford OX3 7FZ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul E","family":"Brennan","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Research UK Oxford Drug Discovery Institute, Centre for Medicines Discovery, NDM Research Building, University of Oxford , Roosevelt Drive, Oxford OX3 7FZ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul J","family":"Harrison","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Oxford , Warneford Hospital, Oxford OX3 7JX ,","place":["United Kingdom"]},{"name":"Oxford Health NHS Foundation Trust , Warneford Hospital, Oxford OX3 7JX,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilfried","family":"Haerty","sequence":"additional","affiliation":[{"name":"Earlham Institute , Norwich Research Park, Norwich NR4 7UZ,","place":["United Kingdom"]},{"name":"School of Biological Sciences, University of East Anglia , Norwich Research Park, Norwich NR4 7TJ ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth M","family":"Tunbridge","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Oxford , Warneford Hospital, Oxford OX3 7JX ,","place":["United Kingdom"]},{"name":"Oxford Health NHS Foundation Trust , Warneford Hospital, Oxford OX3 7JX,","place":["United Kingdom"]},{"name":"Boehringer Ingelheim Pharma GmbH & Co. KG , 65 Birkendorfer Stra\u00dfe, 88397, Biberach an der Ri\u00df ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,12,4]]},"reference":[{"key":"2024121018575228400_ref1","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with alphafold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"2024121018575228400_ref2","doi-asserted-by":"publisher","first-page":"102209","DOI":"10.1016\/j.jbc.2022.102209","article-title":"Structural\/functional studies of trio provide insights into its configuration and show that conserved linker elements enhance its activity for rac1","volume":"298","author":"Bandekar","year":"2022","journal-title":"J Biol 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