Rab GTPases control membrane traffic and organelle identity. They are activated and inactivated by Rab effectors, guanine exchange factors (GEFs) and GTPase-activating proteins (GAPs), respectively. Rab5 is involved in early endosome fusion, and is thought to maintain a high activity at these endosomes by recruiting its own effector rabaptin5 (Rbpt5) and its GEF Rabex5; this cascade is considered a prime example of a positive feedback Rab activation loop. Because Rbpt5 also interacts with Rab4 and Rabex5, Martin Spiess and colleagues (p. 4126) set out to analyse its function in greater detail by assessing the effects of deleting individual interaction domains. Unexpectedly, they find that Rbpt5 is not recruited to early endosomes by Rab5, but by Rab4 and through the ubiquitin-interaction domain of Rabex5. This raises the possibility that Rbpt5–Rabex5 is released from the maturing endosome upon deubiquitylation and internalisation of its cargo or when Rab4-GTP levels decrease, thus providing an attractive mechanism for terminating Rab5 activation. Furthermore, lack of the Rab5-binding site in Rbpt5 or silencing of Rab5 expression results in large endosomes that contain early and late endosomal markers, which suggests that endosome maturation requires the transition from Rab4 to Rab5. Taken together, the data presented here challenge the commonly held view of a simple feedback cascade for Rab activation, and provide new important insights into the role of Rab4 and Rab5 in endosome maturation.
A new view of Rab5 activation
- Split-screen
- Views Icon Views
-
Article Versions Icon
Versions
- Version of Record 15 November 2015
- Share Icon Share
-
Tools Icon
Tools
- Search Site
A new view of Rab5 activation. J Cell Sci 15 November 2015; 128 (22): e2201. doi:
Download citation file:
Advertisement
Cited by
Call for papers - Cilia and Flagella: from Basic Biology to Disease
We are welcoming submissions for our upcoming special issue: Cilia and Flagella: from Basic Biology to Disease. This issue will be coordinated by two Guest Editors: Pleasantine Mill (University of Edinburgh) and Lotte Pedersen (University of Copenhagen). Submission deadline: 1 March 2025.
Biologists @ 100 - join us in Liverpool in March 2025
We are excited to invite you to a unique scientific conference, celebrating the 100-year anniversary of The Company of Biologists, and bringing together our different communities. The conference will incorporate the Spring Meetings of the BSCB and the BSDB, the JEB Symposium Sensory Perception in a Changing World and a DMM programme on antimicrobial resistance. Find out more and register your interest to join us in March 2025 in Liverpool, UK.
Principles and regulation of mechanosensing
Mechanics play a fundamental role in cell physiology and represent physical mechanisms which cells use to influence function from the molecular to tissue scale. In this Review, Stefano Sala and colleagues clearly define mechanosensing and mechanotransduction, illustrate various mechanosensing mechanisms and discuss methods that cells use to regulate these processes.
JCS-FocalPlane Training Grants
Early-career researchers - working in an area covered by JCS - who would like to attend a microscopy training course, please apply. Deadline dates for 2024 applications: 7 September (decision by week commencing 8 October 2024); 22 November (decision by week commencing 16 December).
HIV-1 assembly – when virology meets biophysics
Claire Lacouture and colleagues review mechanisms of assembly of the HIV-1 structural protein Gag from biophysical and biological perspectives. The researchers highlight how HIV-1 Gag hijacks host cell factors associated with cortical actin machinery to make new viral particles.