1. SNARE chaperone Sly1 directly mediates close-range vesicle tethering.
- Author
-
Duan M, Plemel RL, Takenaka T, Lin A, Delgado BM, Nattermann U, Nickerson DP, Mima J, Miller EA, and Merz AJ
- Subjects
- Animals, Golgi Apparatus genetics, Golgi Apparatus metabolism, Mammals metabolism, Molecular Chaperones genetics, Molecular Chaperones metabolism, Munc18 Proteins analysis, Munc18 Proteins genetics, Munc18 Proteins metabolism, SNARE Proteins genetics, SNARE Proteins metabolism, Vesicular Transport Proteins metabolism, Saccharomyces cerevisiae Proteins genetics, Saccharomyces cerevisiae Proteins metabolism, Cytoplasmic Vesicles metabolism, Saccharomyces cerevisiae cytology, Saccharomyces cerevisiae metabolism
- Abstract
The essential Golgi protein Sly1 is a member of the Sec1/mammalian Unc-18 (SM) family of SNARE chaperones. Sly1 was originally identified through remarkable gain-of-function alleles that bypass requirements for diverse vesicle tethering factors. Employing genetic analyses and chemically defined reconstitutions of ER-Golgi fusion, we discovered that a loop conserved among Sly1 family members is not only autoinhibitory but also acts as a positive effector. An amphipathic lipid packing sensor (ALPS)-like helix within the loop directly binds high-curvature membranes. Membrane binding is required for relief of Sly1 autoinhibition and also allows Sly1 to directly tether incoming vesicles to the Qa-SNARE on the target organelle. The SLY1-20 mutation bypasses requirements for diverse tethering factors but loses this ability if the tethering activity is impaired. We propose that long-range tethers, including Golgins and multisubunit tethering complexes, hand off vesicles to Sly1, which then tethers at close range to initiate trans-SNARE complex assembly and fusion in the early secretory pathway., (© 2024 Duan et al.)
- Published
- 2024
- Full Text
- View/download PDF