The VPS9-family GEF VINE activates Ypt10 in a late endosomal Rab cascade
- 1Department of Medical Genetics, University of British Columbia, Vancouver BC V6H 3N1
- 2Centre for Molecular Medicine and Therapeutics, British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver BC V5Z 4H4
Abstract
Rab GTPase cascades drive endosomal membrane maturation by sequentially activating and inactivating Rab proteins. These transitions in Rab signaling require the coordinated actions of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). The yeast VINE complex is an endosomal VPS9-family GEF that stimulates a GAP to inactivate the Rab5 homologue Vps21, suggesting a role for VINE in coordinating Rab transitions. Here we report that VINE acts through its catalytic GEF domain to positively regulate the Rab5-related GTPase Ypt10 and establish a pool of Ypt10 at late endosomes. Ypt10 activation occurs downstream of Vps21 activity, placing Ypt10 within a late endosomal Rab cascade. Genome-wide protein-protein interaction screens revealed a VINE-dependent proximity interaction between Ypt10 and the GEF Mon1-Ccz1. Our data suggest that VINE and Ypt10 regulate late endosomal recruitment of Mon1-Ccz1 to enhance the activation of its substrate, the Rab7 homolog Ypt7. Together, these findings define a Vps21-VINE-Ypt10 regulatory module that adds a layer of control within the late endosomal Vps21-to-Ypt7 cascade and establishes VINE as a dual Rab regulator. Through opposing activities on Vps21 and Ypt10, VINE may couple Rab5 inactivation to Mon1-Ccz1 recruitment to provide more precise control of degradative protein traffic to the vacuole.
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BibTeX
@article{frier2026vps9family,
title = {{The VPS9-family GEF VINE activates Ypt10 in a late endosomal Rab cascade}},
author = {Mia S. Frier and Michael Davey and Elizabeth Conibear},
journal = {Molecular Biology of the Cell},
year = {2026},
month = oct,
doi = {10.1091/mbc.e26-07-0303},
url = {https://doi.org/10.1091/mbc.e26-07-0303},
note = {CC BY-NC-SA 4.0},
}
RIS
TY - JOUR
TI - The VPS9-family GEF VINE activates Ypt10 in a late endosomal Rab cascade
AU - Mia S. Frier
AU - Michael Davey
AU - Elizabeth Conibear
PY - 2026
DA - 2026/10/26
JO - Molecular Biology of the Cell
DO - 10.1091/mbc.e26-07-0303
UR - https://doi.org/10.1091/mbc.e26-07-0303
AB - Rab GTPase cascades drive endosomal membrane maturation by sequentially activating and inactivating Rab proteins. These transitions in Rab signaling require the coordinated actions of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). The yeast VINE complex is an endosomal VPS9-family GEF that stimulates a GAP to inactivate the Rab5 homologue Vps21, suggesting a role for VINE in coordinating Rab transitions. Here we report that VINE acts through its catalytic GEF domain to positively regulate the Rab5-related GTPase Ypt10 and establish a pool of Ypt10 at late endosomes. Ypt10 activation occurs downstream of Vps21 activity, placing Ypt10 within a late endosomal Rab cascade. Genome-wide protein-protein interaction screens revealed a VINE-dependent proximity interaction between Ypt10 and the GEF Mon1-Ccz1. Our data suggest that VINE and Ypt10 regulate late endosomal recruitment of Mon1-Ccz1 to enhance the activation of its substrate, the Rab7 homolog Ypt7. Together, these findings define a Vps21-VINE-Ypt10 regulatory module that adds a layer of control within the late endosomal Vps21-to-Ypt7 cascade and establishes VINE as a dual Rab regulator. Through opposing activities on Vps21 and Ypt10, VINE may couple Rab5 inactivation to Mon1-Ccz1 recruitment to provide more precise control of degradative protein traffic to the vacuole.
SN - 1059-1524
SN - 1939-4586
ER -