Loading…

Rab GAP cascade defines the boundary between two Rab GTPases on the secretory pathway

Membrane traffic along the endocytic and exocytic pathways relies on the appropriate localization and activation of a series of different Rab GTPases. Rabs are activated by specific guanine nucleotide exchange factors (GEFs) and inactivated by GTPase-activating proteins (GAPs). GEF cascades, in whic...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2009-08, Vol.106 (34), p.14408-14413
Main Authors: Rivera-Molina, Félix E, Novick, Peter J
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Membrane traffic along the endocytic and exocytic pathways relies on the appropriate localization and activation of a series of different Rab GTPases. Rabs are activated by specific guanine nucleotide exchange factors (GEFs) and inactivated by GTPase-activating proteins (GAPs). GEF cascades, in which one Rab in its GTP-bound form recruits the GEF that activates the next Rab along the pathway, can account for the sequential activation of a series of Rabs, but it does not explain how the first Rab is inactivated after the next Rab has been activated. We present evidence for a counter-current GAP cascade that serves to restrict the spatial and temporal overlap of 2 Rabs, Ypt1p and Ypt32p, on the exocytic pathway in Saccharomyces cerevisiae. We show that Gyp1p, a GAP for Ypt1p, specifically interacts with Ypt32p, and that this interaction is important for the localization and stability of Gyp1p. Moreover, we demonstrate that, in WT cells, Ypt1p compartments are converted over time into Ypt32p compartments, whereas in gyp1Δ cells there is a significant increase in compartments containing both proteins that reflects a slower transition from Ypt1p to Ypt32p. GEF cascades working in concert with counter-current GAP cascades could generate a programmed series of Rab conversions responsible for regulating the choreography of membrane traffic.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0906536106