Phosphorylation of Ykt6 SNARE Domain Regulates Its Membrane Recruitment and Activity.

Biomolecules
Pradhipa Karuna MJulia Christina Gross

Abstract

Sensitive factor attachment protein receptors (SNARE) proteins are important mediators of protein trafficking that regulate the membrane fusion of specific vesicle populations and their target organelles. The SNARE protein Ykt6 lacks a transmembrane domain and attaches to different organelle membranes. Mechanistically, Ykt6 activity is thought to be regulated by a conformational change from a closed cytosolic form to an open membrane-bound form, yet the mechanism that regulates this transition is unknown. We identified phosphorylation sites in the SNARE domain of Ykt6 that mediate Ykt6 membrane recruitment and are essential for cellular growth. Using proximity-dependent labeling and membrane fractionation, we found that phosphorylation regulates Ykt6 conversion from a closed to an open conformation. This conformational switch recruits Ykt6 to several organelle membranes, where it functionally regulates the trafficking of Wnt proteins and extracellular vesicle secretion in a concentration-dependent manner. We propose that phosphorylation of its SNARE domain leads to a conformational switch from a cytosolic, auto-inhibited Ykt6 to an active SNARE at different membranes.

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Citations

Mar 17, 2021·Proceedings of the National Academy of Sciences of the United States of America·Kaitlyn McGrathGabriela Caraveo

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Datasets Mentioned

BETA
GM130

Methods Mentioned

BETA
X-ray
PCR
transgenic
Assay
Pull Down
pulldown
pull-down
ubiquitination
acylation

Software Mentioned

ProteinPilot
Netphos
Analyst TF
PeakView
Fiji
Cytoscape
SWATH
ImageJ
PANTHER

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