Phosphorylation of Syntaxin‐1a by casein kinase 2α (CK2α) regulates presynaptic vesicle exocytosis from the reserve pool

Shi, Vanilla (Hua); Craig, Tim J.; Bishop, Paul; Nakamura, Yasuko; Rocca, Dan; Wilkinson, Kevin A.; Henley, Jeremy M.

Abstract

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.

• Journal Article Type: Article
• Acceptance Date: Aug 17, 2020
• Online Publication Date: Aug 27, 2020
• Publication Date: Mar 1, 2021
• Deposit Date: Sep 4, 2020
• Publicly Available Date: Apr 8, 2021
• Journal: Journal of Neurochemistry
• Print ISSN: 0022-3042
• Electronic ISSN: 1471-4159
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 156
• Issue: 5
• Pages: 614-623
• DOI: https://doi.org/10.1111/jnc.15161
• Keywords: Biochemistry; Cellular and Molecular Neuroscience; Casein kinase 2α; Phosphorylation Syntaxin‐1; Vesicle exocytosis
• Public URL: https://uwe-repository.worktribe.com/output/6650867
• Publisher URL: https://onlinelibrary.wiley.com/doi/full/10.1111/jnc.15161
• Additional Information: Published: 2020-08-27