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Phosphorylation of Ykt6 SNARE Domain Regulates Its Membrane Recruitment and Activity
- Source :
- Biomolecules, Biomolecules, Vol 10, Iss 1560, p 1560 (2020), Volume 10, Issue 11
- Publication Year :
- 2020
- Publisher :
- MDPI, 2020.
-
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.
- Subjects :
- Conformational change
lcsh:QR1-502
Biochemistry
Membrane Fusion
lcsh:Microbiology
Article
Animals, Genetically Modified
R-SNARE Proteins
03 medical and health sciences
0302 clinical medicine
Ykt6 conformational switch
Organelle
Animals
Drosophila Proteins
Humans
Secretion
Amino Acid Sequence
Phosphorylation
Molecular Biology
Secretory pathway
030304 developmental biology
0303 health sciences
Chemistry
Lipid bilayer fusion
Extracellular vesicle
HCT116 Cells
Cell biology
secretory pathway
Transmembrane domain
HEK293 Cells
membrane attachment
Drosophila
protein trafficking
SNARE Proteins
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 2218273X
- Volume :
- 10
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Biomolecules
- Accession number :
- edsair.doi.dedup.....1203da5a3a89a0452d52e30b211fd82a