Rab-Effector-Kinase Interplay Modulates Intralumenal Fragment Formation during Vacuole Fusion

Upon vacuolar lysosome (or vacuole) fusion in S. cerevisiae, a portion of membrane is internalized and catabolized. Formation of this intralumenal fragment (ILF) is important for organelle protein and lipid homeostasis and remodeling. But how ILF formation is optimized for membrane turnover is not u...

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Bibliographic Details
Published in:Developmental cell Vol. 47; no. 1; p. 80
Main Authors: Karim, Mahmoud Abdul, McNally, Erin Kate, Samyn, Dieter Ronny, Mattie, Sevan, Brett, Christopher Leonard
Format: Journal Article
Language:English
Published: United States 08.10.2018
Subjects:
Casein Kinase I - metabolism
Homeostasis
Lipid Bilayers
Lipid Metabolism
Lipids - physiology
Lysosomes
Membrane Fusion - physiology
Permeability
Phosphorylation
Phosphotransferases
Proteolysis
rab GTP-Binding Proteins - genetics
rab GTP-Binding Proteins - metabolism
rab GTP-Binding Proteins - physiology
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
Saccharomyces cerevisiae Proteins - physiology
Vacuoles - metabolism
Vacuoles - physiology
Vesicular Transport Proteins - genetics
Vesicular Transport Proteins - metabolism
Vesicular Transport Proteins - physiology
hemifusion
vacuole
SNAREs
homotypic vacuole fusion
Rab-GTPase
HOPS
lysosome
protein degradation
intralumenal fragment
membrane fusion
ISSN:1878-1551, 1878-1551
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Summary:Upon vacuolar lysosome (or vacuole) fusion in S. cerevisiae, a portion of membrane is internalized and catabolized. Formation of this intralumenal fragment (ILF) is important for organelle protein and lipid homeostasis and remodeling. But how ILF formation is optimized for membrane turnover is not understood. Here, we show that fewer ILFs form when the interaction between the Rab-GTPase Ypt7 and its effector Vps41 (a subunit of the tethering complex HOPS) is interrupted by a point mutation (Ypt7-D44N). Subsequent phosphorylation of Vps41 by the casein kinase Yck3 prevents stabilization of trans-SNARE complexes needed for lipid bilayer pore formation. Impairing ILF formation prevents clearance of misfolded proteins from vacuole membranes and promotes organelle permeability and cell death. We propose that HOPS coordinates Rab, kinase, and SNARE cycles to modulate ILF size during vacuole fusion, regulating lipid and protein turnover important for quality control and membrane integrity.
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ISSN:1878-1551
1878-1551
DOI:10.1016/j.devcel.2018.09.002