Molecular mechanisms of synaptic vesicle biogenesis
Abstract/Contents
- Abstract
- Synaptic vesicles (SVs) are secretory vesicles crucial to neuronal communication. Here we investigated the molecular mechanisms underlying somatic SV biogenesis. In C. elegans, we showed that the conserved ARF-like small GTPase ARL-8/Arl8 serves as a master regulator in SV proteins' journey from the Golgi to axonally transported SVs. ARL-8 facilitates SV biogenesis by promoting the sorting of SV proteins into SVs. In strong loss-of-function arl-8 mutants, SV proteins were mis-sorted to degradative compartments, and fewer SVs were generated. We further demonstrated that ARL-8 is localized to membranes and activated by part of the BLOC-1-related complex (BORC), with the SAM-4/Myrlysin subunit displaying GEF activity towards ARL-8. In addition to ARL-8, we present one of the first evidence to implicate sorting nexins 1 (SNX-1/SNX1) and 6 (SNX-6/SNX6) in synaptic protein sorting and function. Both SNXs localized to early endosomes in the soma. Loss of the SNXs decreased synaptic localization of the SV protein SNB-1 as well as endosomal localization of the early endosome protein RAB-5. Functionally, SNX-6 is required for normal synaptic transmission, as its loss-of-function mutant demonstrated aldicarb resistance. Together, our results establish ARL-8 as well as SNX-1 and SNX-6 to be novel regulators of SV biogenesis and implicate a model in which they inhibit non-SV fate and promote SV fate for SV cargoes, respectively.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2021; ©2021 |
| Publication date | 2021; 2021 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Lu, Sharon Yuan-Fu |
|---|---|
| Degree supervisor | Shen, Kang, 1972- |
| Thesis advisor | Shen, Kang, 1972- |
| Thesis advisor | McConnell, Susan K |
| Thesis advisor | Pfeffer, Suzanne |
| Thesis advisor | Wang, Xinnan |
| Degree committee member | McConnell, Susan K |
| Degree committee member | Pfeffer, Suzanne |
| Degree committee member | Wang, Xinnan |
| Associated with | Stanford University, Neurosciences Program |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Sharon Lu. |
|---|---|
| Note | Submitted to the Neurosciences Program. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | https://purl.stanford.edu/jn418kq3180 |
Access conditions
- Copyright
- © 2021 by Sharon Yuan-Fu Lu
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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