{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T21:03:33Z","timestamp":1768511013297,"version":"3.49.0"},"posted":{"date-parts":[[2024,5,20]]},"group-title":"Neuroscience","reference-count":76,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,5,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Sensory hair cells of the inner ear utilize specialized ribbon synapses to transmit sensory stimuli to the central nervous system. This sensory transmission necessitates rapid and sustained neurotransmitter release, which relies on a large pool of synaptic vesicles at the hair-cell presynapse. Work in neurons has shown that kinesin motor proteins traffic synaptic material along microtubules to the presynapse, but how new synaptic material reaches the presynapse in hair cells is not known. We show that the kinesin motor protein Kif1a and an intact microtubule network are necessary to enrich synaptic vesicles at the presynapse in hair cells. We use genetics and pharmacology to disrupt Kif1a function and impair microtubule networks in hair cells of the zebrafish lateral-line system. We find that these manipulations decrease synaptic-vesicle populations at the presynapse in hair cells. Using electron microscopy, along with\n                  <jats:italic>in vivo<\/jats:italic>\n                  calcium imaging and electrophysiology, we show that a diminished supply of synaptic vesicles adversely affects ribbon-synapse function.\n                  <jats:italic>Kif1a<\/jats:italic>\n                  mutants exhibit dramatic reductions in spontaneous vesicle release and evoked postsynaptic calcium responses. Additionally, we find that\n                  <jats:italic>kif1a<\/jats:italic>\n                  mutants exhibit impaired rheotaxis, a behavior reliant on the ability of hair cells in the lateral line to respond to sustained flow stimuli. Overall, our results demonstrate that Kif1a-based microtubule transport is critical to enrich synaptic vesicles at the active zone in hair cells, a process that is vital for proper ribbon-synapse function.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Key points:<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>Kif1a mRNAs are present in zebrafish hair cells<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Loss of Kif1a disrupts the enrichment of synaptic vesicles at ribbon synapses<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Disruption of microtubules depletes synaptic vesicles at ribbon synapses<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Kif1a mutants have impaired ribbon-synapse and sensory-system function<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2024.05.20.595037","type":"posted-content","created":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T23:40:11Z","timestamp":1716248411000},"source":"Crossref","is-referenced-by-count":2,"title":["Kif1a and intact microtubules maintain synaptic-vesicle populations at ribbon synapses in zebrafish hair cells"],"prefix":"10.64898","author":[{"given":"Sandeep","family":"David","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Pinter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keziah-Khue","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David S.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengchang","family":"Lei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuliya","family":"Sokolova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5231-2450","authenticated-orcid":false,"given":"Lavinia","family":"Sheets","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1065-8215","authenticated-orcid":false,"given":"Katie S.","family":"Kindt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024052308050786000_2024.05.20.595037v1.1","doi-asserted-by":"publisher","DOI":"10.1007\/s003590050351"},{"key":"2024052308050786000_2024.05.20.595037v1.2","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.087635"},{"key":"2024052308050786000_2024.05.20.595037v1.3","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3411-05.2005"},{"key":"2024052308050786000_2024.05.20.595037v1.4","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-34-10832.2003"},{"key":"2024052308050786000_2024.05.20.595037v1.5","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1705-12.2012"},{"key":"2024052308050786000_2024.05.20.595037v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(00)00168-4"},{"key":"2024052308050786000_2024.05.20.595037v1.7","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-18-07013.2001"},{"key":"2024052308050786000_2024.05.20.595037v1.8","doi-asserted-by":"crossref","unstructured":"Gallimore AR , Hepburn I , Rizzoli S & Schutter ED (2023). 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