| First Author | Wong MY | Year | 2018 |
| Journal | Proc Natl Acad Sci U S A | Volume | 115 |
| Issue | 9 | Pages | 2234-2239 |
| PubMed ID | 29439199 | Mgi Jnum | J:265782 |
| Mgi Id | MGI:6120581 | Doi | 10.1073/pnas.1719012115 |
| Citation | Wong MY, et al. (2018) Liprin-alpha3 controls vesicle docking and exocytosis at the active zone of hippocampal synapses. Proc Natl Acad Sci U S A 115(9):2234-2239 |
| abstractText | The presynaptic active zone provides sites for vesicle docking and release at central nervous synapses and is essential for speed and accuracy of synaptic transmission. Liprin-alpha binds to several active zone proteins, and loss-of-function studies in invertebrates established important roles for Liprin-alpha in neurodevelopment and active zone assembly. However, Liprin-alpha localization and functions in vertebrates have remained unclear. We used stimulated emission depletion superresolution microscopy to systematically determine the localization of Liprin-alpha2 and Liprin-alpha3, the two predominant Liprin-alpha proteins in the vertebrate brain, relative to other active-zone proteins. Both proteins were widely distributed in hippocampal nerve terminals, and Liprin-alpha3, but not Liprin-alpha2, had a prominent component that colocalized with the active-zone proteins Bassoon, RIM, Munc13, RIM-BP, and ELKS. To assess Liprin-alpha3 functions, we generated Liprin-alpha3-KO mice by using CRISPR/Cas9 gene editing. We found reduced synaptic vesicle tethering and docking in hippocampal neurons of Liprin-alpha3-KO mice, and synaptic vesicle exocytosis was impaired. Liprin-alpha3 KO also led to mild alterations in active zone structure, accompanied by translocation of Liprin-alpha2 to active zones. These findings establish important roles for Liprin-alpha3 in active-zone assembly and function, and suggest that interplay between various Liprin-alpha proteins controls their active-zone localization. |
