Abstract

The Ras-superfamily of small G proteins is a family of GTP hydrolases that is regulated by GTP/GDP binding states. One member of the Ras-superfamily, Rab, is involved in the regulation of vesicle trafficking, which is critical to endocytosis, biosynthesis, secretion, cell differentiation and cell growth. The active form of the Rab proteins, which contains GTP, can recruit specific binding partners, such as sorting adaptors, tethering factors, kinases, phosphatases and motor proteins, thereby influencing vesicle formation, transport, and tethering. Many Rab proteins share the same interacting partners and perform unique roles in specific locations. Because functional loss of the Rab pathways has been implicated in a variety of diseases, the Rab GTPase family has been extensively investigated. In this review, we summarize Rab GTPase- mediated membrane trafficking while focusing on the structures of Rab protein and Rab-effector complexes. This review provides detailed information that helps explain how the Rab GTPase family is involved in membrane trafficking.

Highlights

  • Small GTPase proteins including the Ras-superfamily of small G proteins are involved in membrane trafficking [1,2,3,4]

  • Changing between GDP and GTP is controlled by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs) [4,15,16,17]

  • A few effectors can interact with a GDP-bound inactive form of Rab, most effectors bind to GTP-bound active form of Rab and are involved in membrane trafficking [20]

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Summary

Introduction

Small GTPase proteins including the Ras-superfamily of small G proteins are involved in membrane trafficking [1,2,3,4]. The GTP-bound active form of Rab can be recruited to membrane vesicles, where it promotes membrane trafficking by interacting with specific effector proteins (Figure 1A) [18,19]. A few effectors can interact with a GDP-bound inactive form of Rab, most effectors bind to GTP-bound active form of Rab and are involved in membrane trafficking [20]. Many Rab effectors are identified so far They function at different stages of membrane trafficking: Budding, transporting, tethering, and fusion (Figure 1C). At the vesicle movement stage, the well known case is the interaction of Rab with its effector, Rab family interacting protein 2. Rabs can properly execute their various functions by recruiting specific effectors during membrane trafficking; (C) Crystal structure of the Rab6A/GTP complex (PDB ID: 2GIL). Switch I and switch II are importance for GDP-GTP exchanged mediated activity control

Rab GTPases Involved in Membrane Trafficking
Structure of Rab Subfamily
Conclusions
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