SAD-1 kinase controls presynaptic phase separation by relieving SYD-2/Liprin-α autoinhibition.

ABSTRACT: Neuronal development orchestrates the formation of an enormous number of synapses that connect the nervous system. In developing presynapses, the core active zone structure has been found to assemble through a liquid-liquid phase separation. Here, we find that the phase separation of SYD-2/Liprin-α, a key active zone scaffold, is controlled by phosphorylation. Using phosphoproteomics, we identify the SAD-1 kinase to phosphorylate SYD-2 and a number of other substrates. Presynaptic assembly is impaired in sad-1 mutants and increased by overactivation of SAD-1. We determine SAD-1 phosphorylation of SYD-2 at three sites is critical to activate its phase separation. Mechanistically, phosphorylation relieves a binding interaction between two folded SYD-2 domains that inhibits phase separ

SUBMITTER: McDonald NA 

PROVIDER: S-EPMC10312667 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature