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Phosphorylation of Syntaxin‐1a by casein kinase 2α regulates pre‐synaptic vesicle exocytosis from the reserve pool
Author(s) -
Shi Vanilla Hua,
Craig Tim J.,
Bishop Paul,
Nakamura Yasuko,
Rocca Dan,
Wilkinson Kevin A.,
Henley Jeremy M.
Publication year - 2021
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.15161
Subject(s) - munc 18 , exocytosis , synaptic vesicle , microbiology and biotechnology , vesicle fusion , stx1a , casein kinase 2 , casein kinase 1 , biology , kiss and run fusion , synaptotagmin 1 , vesicle , phosphorylation , synaptic vesicle recycling , snap25 , neurotransmitter , chemistry , syntaxin , protein kinase a , biochemistry , secretion , receptor , mitogen activated protein kinase kinase , membrane
The t‐soluble NSF‐attachment protein receptor protein Syntaxin‐1a (Stx‐1a) is abundantly expressed at pre‐synaptic terminals where it plays a critical role in the exocytosis of neurotransmitter‐containing synaptic vesicles. Stx‐1a is phosphorylated by Casein kinase 2α (CK2α) at Ser14, which has been proposed to regulate the interaction of Stx‐1a and Munc‐18 to control of synaptic vesicle priming. However, the role of CK2α in synaptic vesicle dynamics remains unclear. Here, we show that CK2α over‐expression reduces evoked synaptic vesicle release. Furthermore, shRNA‐mediated knockdown of CK2α in primary hippocampal neurons strongly enhanced vesicle exocytosis from the reserve pool, with no effect on the readily releasable pool of primed vesicles. In neurons in which endogenous Stx‐1a was knocked down and replaced with a CK2α phosphorylation‐deficient mutant, Stx‐1a(D17A), vesicle exocytosis was also increased. These results reveal a previously unsuspected role of CK2α phosphorylation in specifically regulating the reserve synaptic vesicle pool, without changing the kinetics of release from the readily releasable pool.