{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:51:41Z","timestamp":1772160701322,"version":"3.50.1"},"reference-count":85,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100007225","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["107\u20102311\u2010B\u2010007\u2010003\u2010"],"award-info":[{"award-number":["107\u20102311\u2010B\u2010007\u2010003\u2010"]}],"id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Kinesin\u20103 UNC\u2010104(KIF1A) is the major anterograde axonal transporter of synaptic vesicles and is expressed pan\u2010neuronally. Genetic defects in this molecular motor are linked to KIF1A\u2010associated neurological disorders (KAND), a spectrum of severe neurological conditions encompassing Charcot\u2013Marie\u2010Tooth (CMT) disease and hereditary spastic paraplegia (HSP). From a candidate screen for genes causing neurotransmission defects in\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>C. elegans<\/jats:italic>\n                    <\/jats:styled-content>\n                    and simultaneously affecting post\u2010translational modification of tubulin, we identified allele\n                    <jats:italic>unc\u201017<\/jats:italic>\n                    (\n                    <jats:italic>e245<\/jats:italic>\n                    ) significantly elevating tubulin acetylation in\u00a0vitro and in\u00a0vivo. UNC\u201017 encodes for a VAChT (vesicular acetylcholine transporter) and its human ortholog SLC18A3 is implicated in Alzheimer's and Huntington's disease. To exclude secondary effects of the\n                    <jats:italic>unc\u201017<\/jats:italic>\n                    mutation, we tracked UNC\u2010104 and RAB\u20103 motility in the non\u2010cholinergic ALM neuron. With upregulated tubulin acetylation in ALM (anterior lateral microtubule) neurons in\n                    <jats:italic>unc\u201017<\/jats:italic>\n                    (\n                    <jats:italic>e245<\/jats:italic>\n                    ) strains (visualized by immunostaining), motility of both motor and its cargo is significantly compromised. However, motility of UNC\u2010104 improves when knocking down \u03b1\u2010tubulin acetyltransferase MEC\u201017(ATAT1) in\n                    <jats:italic>unc\u201017<\/jats:italic>\n                    (\n                    <jats:italic>e245<\/jats:italic>\n                    ) strains and, conversely, is negatively affected when overexpressing MEC\u201017 in wild type animals. Similar effects were observed in cholinergic sublaterals. UNC\u201017 and UNC\u2010104 colocalize in cholinergic head neurons, consistent with a motor\u2010cargo relationship. Strikingly,\n                    <jats:italic>mec\u201017<\/jats:italic>\n                    knockdown significantly decreases their colocalization, while\n                    <jats:italic>unc\u201017<\/jats:italic>\n                    knockdown reduces UNC\u2010104\/MEC\u201017 colocalization in head neurons. Direct protein\u2013protein interactions were validated through bimolecular fluorescence complementation (BiFC) and co\u2010immunoprecipitation (Co\u2010IP) assays. In both assays,\n                    <jats:italic>mec\u201017<\/jats:italic>\n                    knockdown significantly reduced the UNC\u2010104\/UNC\u201017 associations, whereas\n                    <jats:italic>unc\u201017<\/jats:italic>\n                    knockdown significantly diminished UNC\u2010104\/MEC\u201017 interactions. These findings indicate a tripartite regulatory complex UNC\u2010104\/UNC\u201017\/MEC\u201017. We propose that\n                    <jats:italic>unc\u201017<\/jats:italic>\n                    knockdown disrupts sequestration of MEC\u201017 within this complex and that the release of MEC\u201017 results in increased tubulin acetylation. Resulting elevated tubulin acetylation suppresses UNC\u2010104 motor processivity and cargo transport efficiency.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70322-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70322","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T15:37:42Z","timestamp":1766763462000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Mutation in Vesicular Acetylcholine Transporter Increases Tubulin Acetylation Compromising Synaptic Vesicle Transport"],"prefix":"10.1111","volume":"169","author":[{"given":"Cheng\u2010Shan","family":"Kuo","sequence":"first","affiliation":[{"name":"Department of Life Science Institute of Molecular and Cellular Biology, National Tsing Hua University  Hsinchu Taiwan, ROC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vignesh Mahendran","family":"Ruckmani","sequence":"additional","affiliation":[{"name":"Department of Life Science Institute of Molecular and Cellular Biology, National Tsing Hua University  Hsinchu Taiwan, ROC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng\u2010Chieh","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Life Science Institute of Molecular and Cellular Biology, National Tsing Hua University  Hsinchu Taiwan, ROC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad Safwan","family":"Khawaja","sequence":"additional","affiliation":[{"name":"Department of 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