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Phosphorylation of residues inside the SNARE complex suppresses secretory vesicle fusion
Author(s) -
Malmersjö Seth,
Di Palma Serena,
Diao Jiajie,
Lai Ying,
Pfuetzner Richard A,
Wang Austin L,
McMahon Moira A,
Hayer Arnold,
Porteus Matthew,
Bodenmiller Bernd,
Brunger Axel T,
Meyer Tobias
Publication year - 2016
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201694071
Subject(s) - biology , phosphorylation , vesicle , secretory vesicle , microbiology and biotechnology , vesicle fusion , lipid bilayer fusion , exocytosis , biochemistry , secretion , synaptic vesicle , membrane
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 VAMP 8 becomes phosphorylated by PKC at multiple residues in the SNARE domain. Our data suggest that VAMP 8 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 VAMP s, but present in all other VAMP s. 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.