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Rab GEFs and GAPs: The Enigma Variations

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Ras Superfamily Small G Proteins: Biology and Mechanisms 2

Abstract

Rab GTPases are key regulators of membrane traffic activated on the surface of organelle and vesicle membranes during vesicle trafficking events, cell polarisation and autophagy. Rabs undergo a cycle of activation involving GTP binding and inactivation involving GTP hydrolysis in response to cellular regulators. Each Rab has a cognate GDP–GTP exchange factor (GEF) promoting release of GDP and subsequent binding of GTP, and a GTPase activating protein (GAP) stimulating the slow intrinsic GTP hydrolysis. Together these GEF and GAP regulators determine when and where a specific Rab is activated, and how long its activity will persist. Rab GEFs fall into a number of discrete families, the largest of which are the Vps9 domain, DENN and DENN domain-related proteins. Other Rab GEF families, including TRAPP, Ric1-Rgp1, Mon1-Ccz1 and Hps1-Hps4, are comprised of two or more polypeptide chains. By contrast, almost all known Rab GAPs possess a TBC1 domain. Here I will discuss the mechanisms by which these GEFs and GAPs regulate Rab GTPases, highlighting common themes and points of difference, and briefly outlining the cellular processes they regulate.

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  1. Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK

    Francis A. Barr

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    Alfred Wittinghofer

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Barr, F.A. (2014). Rab GEFs and GAPs: The Enigma Variations. In: Wittinghofer, A. (eds) Ras Superfamily Small G Proteins: Biology and Mechanisms 2. Springer, Cham. https://doi.org/10.1007/978-3-319-07761-1_5

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