Coupled activation and inactivation of endosomal Rab GTPases

Tuesday, 9 June 2026, 10am to 11am

Small GTPases in the Rab5 family maintain the composition and function of the plasma membrane, Golgi, endosomes, and lysosomes by coordinating vesicular trafficking between these organelles. The membrane targeting of Rab5 regulators determines the precise contexts in which each Rab5 GTPase governs endolysosomal trafficking events. Study of two exchange factors that positively regulate Rab5-family GTPases in the model eukaryote budding yeast have uncovered mechanisms linking Rab5 signaling to membrane protein sorting and trafficking. We have discovered two unique modes of Rab regulation by the third Rab5 exchange factor in yeast, the endosomal complex VINE. Despite being a positive regulator of Rab5-family proteins, VINE triggers the inactivation of the major yeast Rab5 homolog. Findings from genome-wide protein proximity screening, mutagenesis guided by predictive structural modelling, and in vivo assays have given rise to a model in which VINE forms a novel protein phosphatase 1 complex that acts on known Vps21 negative regulators to promote Vps21 inactivation. We have also identified a minor Rab5 homolog as a target of positive regulation by VINE. Its interactome implicates this GTPase in modulating endosomal membrane maturation and trafficking to the lysosome-related vacuole. This work reveals a direct link between positive and negative Rab regulation which may allow VINE to transform Rab signaling during endosomal protein trafficking events.

Speaker(s): Mia Frier (PhD Candidate, Department of Medical Genetics, The University of British Columbia)

Series: Seminar

Venue: Dorothy Crowfoot Hodgkin Building - DCHB 20-138 Seminar Room 2 - DCHB 20-138 Seminar Room 2 Dorothy Crowfoot Hodgkin Building off South Parks Road Oxford Oxfordshire OX1 3QU United Kingdom

Department: Biochemistry (Department)

Organiser: Haoxi Wu

Host: Dr Haoxi Wu