Liprin-?3 controls vesicle docking and exocytosis at the active zone of hippocampal synapses.

ABSTRACT: 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-? binds to several active zone proteins, and loss-of-function studies in invertebrates established important roles for Liprin-? in neurodevelopment and active zone assembly. However, Liprin-? localization and functions in vertebrates have remained unclear. We used stimulated emission depletion superresolution microscopy to systematically determine the localization of Liprin-?2 and Liprin-?3, the two predominant Liprin-? proteins in the vertebrate brain, relative to other active-zone proteins. Both proteins were widely distributed in hippocampal nerve terminals, and Liprin-?3, but not Liprin-?2, had a prominent component that colocalized with the active-zone proteins Bassoon, RIM, Munc13, RIM-BP, and ELKS. To assess Liprin-?3 functions, we generated Liprin-?3-KO mice by using CRISPR/Cas9 gene editing. We found reduced synaptic vesicle tethering and docking in hippocampal neurons of Liprin-?3-KO mice, and synaptic vesicle exocytosis was impaired. Liprin-?3 KO also led to mild alterations in active zone structure, accompanied by translocation of Liprin-?2 to active zones. These findings establish important roles for Liprin-?3 in active-zone assembly and function, and suggest that interplay between various Liprin-? proteins controls their active-zone localization.

SUBMITTER: Wong MY 

PROVIDER: S-EPMC5834710 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature