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Distinct features of multivesicular body-lysosome fusion revealed by a new cell-free content-mixing assay.

Author(s): Karim MA, Samyn DR, Mattie S, Brett CL

Traffic. 2018 02;19(2):138-149 Authors: Karim MA, Samyn DR, Mattie S, Brett CL

Article GUID: 29135058
The Na+(K+)/H+ exchanger Nhx1 controls multivesicular body-vacuolar lysosome fusion.

Author(s): Karim MA, Brett CL

Mol Biol Cell. 2018 02 01;29(3):317-325 Authors: Karim MA, Brett CL

Article GUID: 29212874
Rab-Effector-Kinase Interplay Modulates Intralumenal Fragment Formation during Vacuole Fusion.

Author(s): Karim MA, McNally EK, Samyn DR, Mattie S, Brett CL

Dev Cell. 2018 10 08;47(1):80-97.e6 Authors: Karim MA, McNally EK, Samyn DR, Mattie S, Brett CL

Article GUID: 30269949
A Cell-Free Content Mixing Assay for SNARE-Mediated Multivesicular Body-Vacuole Membrane Fusion.

Author(s): Karim MA, Samyn DR, Brett CL

Methods Mol Biol. 2019;1860:289-301 Authors: Karim MA, Samyn DR, Brett CL

Article GUID: 30317513
Visualization of SNARE-Mediated Organelle Membrane Hemifusion by Electron Microscopy.

Author(s): Mattie S, Kazmirchuk T, Mui J, Vali H, Brett CL

Methods Mol Biol. 2019;1860:361-377 Authors: Mattie S, Kazmirchuk T, Mui J, Vali H, Brett CL

Article GUID: 30317518
The intralumenal fragment pathway mediates ESCRT-independent surface transporter down-regulation.

Author(s): McNally EK, Brett CL

Nat Commun. 2018 12 18;9(1):5358 Authors: McNally EK, Brett CL

Article GUID: 30560896
Title:Rab-Effector-Kinase Interplay Modulates Intralumenal Fragment Formation during Vacuole Fusion.
Authors:Karim MA,  McNally EK,  Samyn DR,  Mattie S,  Brett CL
Link:https://www.ncbi.nlm.nih.gov/pubmed/30269949?dopt=Abstract
DOI:10.1016/j.devcel.2018.09.002
Category:Dev Cell
PMID:30269949
Dept Affiliation: BIOLOGY
1 Department of Biology, Concordia University, 7141 Sherbrooke St. W., SP, 501.15, Montréal, QC H4R 1R6, Canada.
2 Department of Biology, Concordia University, 7141 Sherbrooke St. W., SP, 501.15, Montréal, QC H4R 1R6, Canada. Electronic address: christopher.brett@concordia.ca.

Description:

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

Dev Cell. 2018 10 08;47(1):80-97.e6

Authors: Karim MA, McNally EK, Samyn DR, Mattie S, Brett CL

Abstract

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.

PMID: 30269949 [PubMed - indexed for MEDLINE]