Phosphorylation of Residues Inside the SNARE Complex Suppresses Secretory Vesicle Fusion

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2016 Jul 13

PMID 27402227

Citations 22

Authors

Seth Malmersjo

Serena Di Palma

Jiajie Diao

Ying Lai

Richard A Pfuetzner

Austin L Wang

Moira A McMahon

Arnold Hayer

Matthew Porteus

Bernd Bodenmiller

Axel T Brunger

Tobias Meyer

Affiliations

Soon will be listed here.

Abstract

Membrane fusion is essential for eukaryotic life, requiring SNARE proteins to zipper up in an α-helical bundle to pull two membranes together. Here, we show that vesicle fusion can be suppressed by phosphorylation of core conserved residues inside the SNARE domain. We took a proteomics approach using a PKCB knockout mast cell model and found that the key mast cell secretory protein VAMP8 becomes phosphorylated by PKC at multiple residues in the SNARE domain. Our data suggest that VAMP8 phosphorylation reduces vesicle fusion in vitro and suppresses secretion in living cells, allowing vesicles to dock but preventing fusion with the plasma membrane. Markedly, we show that the phosphorylation motif is absent in all eukaryotic neuronal VAMPs, but present in all other VAMPs. Thus, phosphorylation of SNARE domains is a general mechanism to restrict how much cells secrete, opening the door for new therapeutic strategies for suppression of secretion.

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