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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Veröffentlicht in:	Developmental cell Jg. 47; H. 1; S. 80
Hauptverfasser:	Karim, Mahmoud Abdul, McNally, Erin Kate, Samyn, Dieter Ronny, Mattie, Sevan, Brett, Christopher Leonard
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States 08.10.2018
Schlagworte:	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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Zusammenfassung:	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.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1878-1551 1878-1551
DOI:	10.1016/j.devcel.2018.09.002