{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:51:27Z","timestamp":1790175087852,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T00:00:00Z","timestamp":1389139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001348","name":"Agency for Science, Technology and Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001348","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012415","name":"Biomedical Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012415","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000867","name":"Robert Wood Johnson Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000867","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Gain\u2010of\u2010toxic\u2010function mutations in Seipin (Asparagine 88 to Serine (N88S) and Serine 90 to Leucine (S90L) mutations, both of which disrupt the N\u2010glycosylation) cause autosomal dominant motor neuron diseases. However, the mechanism of how these missense mutations lead to motor neuropathy is unclear. Here, we analyze the impact of disruption of N\u2010glycosylation of Seipin on synaptic transmission by over\u2010expressing mutant Seipin in cultured cortical neurons via lentiviral infection. Immunostaining shows that over\u2010expressed Seipin is partly colocalized with synaptic vesicle marker synaptophysin. Electrophysiological recordings reveal that the Seipin mutation significantly decreases the frequency, but not the amplitudes of miniature excitatory post\u2010synaptic currents and miniature inhibitory post\u2010synaptic currents. The amplitude of both evoked excitatory post\u2010synaptic currents and inhibitory post\u2010synaptic current is also compromised by mutant Seipin over\u2010expression. The readily releasable pool and vesicular release probability of synaptic vesicles are both altered in neurons over\u2010expressing Seipin\u2010N88S, whereas neither \u03b3\u2010amino butyric acid (GABA) nor \u03b1\u2010Amino\u20103\u2010hydroxy\u20105\u2010methyl\u20104\u2010 isoxazolepropionic acid (AMPA) induced whole cell currents are affected. Moreover, electron microscopy analysis reveals decreased number of morphologically docked synaptic vesicles in Seipin\u2010N88S\u2010expressing neurons. These data demonstrate that Seipin\u2010N88S mutation impairs synaptic neurotransmission, possibly by regulating the priming and docking of synaptic vesicles at the synapse.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc12638-fig-0007-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>Motoneuropathy\u2010associated endoplasmic reticulum (ER) protein Seipin\u2010N88S mutation disrupts N\u2010glycosylation and decreased the frequency of miniature excitatory and inhibitory post\u2010synaptic currents (PSCs), and the amplitude of evoked excitatory and inhibitory PSCs. The readily releasable pool and synaptic vesicle (SV) release probability were reduced in neurons over\u2010expressing Seipin\u2010N88S, along with decreased number of docked vesicles. We propose that Seipin\u2010N88S mutation impairs synaptic neurotransmission by regulating the docking of synaptic vesicles.<\/jats:p>","DOI":"10.1111\/jnc.12638","type":"journal-article","created":{"date-parts":[[2013,12,18]],"date-time":"2013-12-18T08:06:41Z","timestamp":1387354001000},"page":"328-338","source":"Crossref","is-referenced-by-count":19,"title":["Motor neuropathy\u2010associated mutation impairs Seipin functions in neurotransmission"],"prefix":"10.1111","volume":"129","author":[{"given":"Shunhui","family":"Wei","sequence":"first","affiliation":[{"name":"Laboratory of Metabolic Medicine Singapore Bioimaging Consortium, A*STAR Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie Li\u2010Ying","family":"Soh","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic Medicine Singapore Bioimaging Consortium, A*STAR Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Xia","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic Medicine Singapore Bioimaging Consortium, A*STAR Singapore"},{"name":"Child Health Institute of New Jersey Department of Neuroscience and Cell Biology Rutgers Robert Wood Johnson Medical School New Brunswick New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Yi","family":"Ong","sequence":"additional","affiliation":[{"name":"Department of Anatomy Yong Loo Lin School of Medicine National University of Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiping P.","family":"Pang","sequence":"additional","affiliation":[{"name":"Child Health Institute of New Jersey Department of Neuroscience and Cell Biology Rutgers Robert Wood Johnson Medical School New Brunswick New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiping","family":"Han","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic Medicine Singapore Bioimaging Consortium, A*STAR Singapore"},{"name":"Institute of Molecular and Cell Biology A*STAR Singapore"},{"name":"Department of Biochemistry Yong Loo Lin School of Medicine National University of Singapore Singapore"},{"name":"Cardiovascular and Metabolic Disorders Program Duke\u2010NUS Graduate Medical School 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