dc.contributor.author | Mahadik, Snehal S. | |
dc.contributor.author | Lundquist, Erik A. | |
dc.date.accessioned | 2023-05-30T16:37:25Z | |
dc.date.available | 2023-05-30T16:37:25Z | |
dc.date.issued | 2023-04-04 | |
dc.identifier.citation | Mahadik, S. S., & Lundquist, E. A. (2023). TOM-1/tomosyn acts with the UNC-6/netrin receptor UNC-5 to inhibit growth cone protrusion in Caenorhabditis elegans. Development (Cambridge, England), 150(7), dev201031. https://doi.org/10.1242/dev.201031 | en_US |
dc.identifier.uri | https://hdl.handle.net/1808/34233 | |
dc.description.abstract | In the polarity/protrusion model of growth cone repulsion from UNC-6/netrin, UNC-6 first polarizes the growth cone of the VD motor neuron axon via the UNC-5 receptor, and then regulates protrusion asymmetrically across the growth cone based on this polarity. UNC-6 stimulates protrusion dorsally through the UNC-40/DCC receptor, and inhibits protrusion ventrally through UNC-5, resulting in net dorsal growth. Previous studies showed that UNC-5 inhibits growth cone protrusion via the flavin monooxygenases and potential destabilization of F-actin, and via UNC-33/CRMP and restriction of microtubule plus-end entry into the growth cone. We show that UNC-5 inhibits protrusion through a third mechanism involving TOM-1/tomosyn. A short isoform of TOM-1 inhibited protrusion downstream of UNC-5, and a long isoform had a pro-protrusive role. TOM-1/tomosyn inhibits formation of the SNARE complex. We show that UNC-64/syntaxin is required for growth cone protrusion, consistent with a role of TOM-1 in inhibiting vesicle fusion. Our results are consistent with a model whereby UNC-5 utilizes TOM-1 to inhibit vesicle fusion, resulting in inhibited growth cone protrusion, possibly by preventing the growth cone plasma membrane addition required for protrusion. | en_US |
dc.publisher | The Company of Biologists | en_US |
dc.rights | © 2023. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | Axon guidance | en_US |
dc.subject | Growth cone | en_US |
dc.subject | TOM-1/tomosyn | en_US |
dc.subject | UNC-5 | en_US |
dc.subject | UNC-6/netrin | en_US |
dc.title | TOM-1/tomosyn acts with the UNC-6/netrin receptor UNC-5 to inhibit growth cone protrusion in Caenorhabditis elegans | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Mahadik, Snehal S. | |
kusw.kuauthor | Lundquist, Erik A. | |
kusw.kudepartment | Molecular Biosciences | en_US |
dc.identifier.doi | 10.1242/dev.201031 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-3840-695X | en_US |
dc.identifier.orcid | https://orcid.org/0000-0001-6819-4815 | en_US |
kusw.oaversion | Scholarly/refereed, publisher version | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC10112904 | en_US |
dc.rights.accessrights | openAccess | en_US |