{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:33:55Z","timestamp":1787319235059,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","issue":"9-10","license":[{"start":{"date-parts":[[2024,5,18]],"date-time":"2024-05-18T00:00:00Z","timestamp":1715990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cytoskeleton"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tau is a microtubule associated protein that plays important roles in regulating the properties of microtubules and axonal transport, as well as tauopathies associated with toxic aggregates leading to neurodegenerative diseases. It is encoded by the MAPT gene forming multiple isoforms (45\u201360\u2009kDa) by alternative splicing which are developmentally regulated. The high molecular weight (MW) tau isoform of 105\u2009kDa, termed Big tau, was originally discovered in the peripheral nervous system (PNS) but later found in selective CNS areas. It contains an additional large exon 4a generating a long projecting domain of about 250 amino acids. Here we investigated the properties of Big tau in the visual system of rats, its distribution in retinal ganglion cells and the optic nerve as well as its developmental regulation using biochemical, molecular and histological analyses. We discovered that Big tau is expresses as a 95\u2009kDa protein (termed middle MW) containing exons 4a, 6 as well as exon 10 which defines a 4 microtubule\u2010binding repeats (4R). It lacks exons 2\/3 but shares the extensive phosphorylation characteristic of other tau isoforms. Importantly, early in development the visual system expresses only the low MW isoform (3R) switching to both the low and middle MW isoforms (4R) in adult retinal ganglion neurons and their corresponding axons. This is a unique structure and expression pattern of Big tau, which we hypothesize is associated with the specific properties of the visual system different from what has been previously described in the PNS and other areas of the nervous system.<\/jats:p>","DOI":"10.1002\/cm.21875","type":"journal-article","created":{"date-parts":[[2024,5,18]],"date-time":"2024-05-18T08:07:38Z","timestamp":1716019658000},"page":"488-499","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The unique properties of Big tau in the visual system"],"prefix":"10.1002","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3187-8740","authenticated-orcid":false,"given":"Itzhak","family":"Fischer","sequence":"first","affiliation":[{"name":"Department of Neurobiology and Anatomy Drexel University College of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Connors","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy Drexel University College of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Bouyer","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy Drexel University College of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy Drexel University College of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-020-03641-5"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21197290"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-11-03601.1996"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-021-02392-2"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903580209"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.590059"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.101482"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.059890"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.10.4378"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.02.017"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2022.1019999"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0052-23.2023"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2020.04.007"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2009.03.002"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.105.3.729"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.100.1.55"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.5.1983"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2023.137330"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1613-6"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.9.4.1381"},{"key":"e_1_2_11_22_1","first-page":"2700","article-title":"Review: Tauopathy in the retina and optic nerve: Does it shadow pathological changes in the brain?","volume":"18","author":"Ho W. 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