Rabs and their effectors: Achieving specificity in membrane traffic
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Edited by William T. Wickner, Dartmouth Medical School, Hanover, NH, and approved June 21, 2006 (received for review February 27, 2006)
Abstract
Rab proteins constitute the largest branch of the Ras GTPase superfamily. Rabs use the guanine nucleotide-dependent switch mechanism common to the superfamily to regulate each of the four major steps in membrane traffic: vesicle budding, vesicle delivery, vesicle tethering, and fusion of the vesicle membrane with that of the target compartment. These different tasks are carried out by a diverse collection of effector molecules that bind to specific Rabs in their GTP-bound state. Recent advances have not only greatly extended the number of known Rab effectors, but have also begun to define the mechanisms underlying their distinct functions. By binding to the guanine nucleotide exchange proteins that activate the Rabs certain effectors act to establish positive feedback loops that help to define and maintain tightly localized domains of activated Rab proteins, which then serve to recruit other effector molecules. Additionally, Rab cascades and Rab conversions appear to confer directionality to membrane traffic and couple each stage of traffic with the next along the pathway.
Footnotes
- †To whom correspondence should be addressed. E-mail: peter.novick{at}yale.edu
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↵*Present address: Novartis Institutes of Biomedical Research, 4002 Basel, Switzerland.
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Author contributions: B.L.G., D.O., and P.N. wrote the paper.
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Conflict of interest statement: No conflicts declared.
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This paper was submitted directly (Track II) to the PNAS office.
- Abbreviations:
- GEF,
- guanine nucleotide exchange factor;
- GAP,
- GTPase-activating protein;
- GDI,
- GDP dissociation inhibitor;
- GDF,
- GDI displacement factor;
- MPR,
- mannose 6-phosphate receptor;
- TIP47,
- tail-interacting protein of 47 kDa;
- EEA1,
- early endosome antigen 1;
- VPS,
- vacuole protein sorting;
- HOPS,
- homotypic fusion and vacuole protein sorting;
- SNARE,
- soluble N-ethylmaleimide-sensitive factor attachment protein receptor;
- PI,
- phosphatidylinositol;
- PI(3)P,
- PI 3-phosphate
- © 2006 by The National Academy of Sciences of the USA
