Rabs and EHDs: alternate modes for traffic control - PubMed (original) (raw)

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Rabs and EHDs: alternate modes for traffic control

Jing Zhang et al. Biosci Rep. 2012 Feb.

Abstract

Endocytic trafficking is a highly organized process regulated by a network of proteins, including the Rab family of small GTP-binding proteins and the C-terminal EHDs (Eps15 homology-domain-containing proteins). Central roles for Rab proteins have been described in vesicle budding, delivery, tethering and fusion, whereas little is known about the functions of EHDs in membrane transport. Common effectors for these two protein families have been identified, and they facilitate regulation of sequential steps in transport. By comparing and contrasting key aspects in their modes of function, we shall promote a better understanding of how Rab proteins and EHDs regulate endocytic trafficking.

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Figures

Figure 1

Figure 1. Schematic diagram of EHD domain architecture

EHDs contain two helical regions with an ATP-binding G domain in between. The C-terminal EH domain is connected with the helical domain by a 40-residue linker region.

Figure 2

Figure 2. Interaction with motor proteins

(A) EHD and dynein. CRMP2 serves as a link between MICAL-L1-EHD1-associated vesicles and cytoplasmic dynein, and mediates microtubule-dependent vesicle transport. (B) Interactions between Rab proteins and either myosin, kinesin or dynein motors through their respective effectors. Rab11 interacts with myosin Vb through Rab11-FIP2, which is also an EHD-binding partner. Rab5 and its effector hVPS34 (human VPS34) regulate KIF16B (kinesin 16B) transportation of PI(3)P [PtdIns(3)_P_]-positive early endosomes. RILP binds to Rab7 and mediates vesicle transport by recruiting the dynein–dynactin complex.

Figure 3

Figure 3. Models of EHDs and Rab proteins

(A) EHD ‘pinchase’ model. EHD-ATP dimers oligomerize along the tubular membrane. ATP hydrolysis induces a conformational change that destabilizes the membrane, which in turn leads to vesicle scission. (B) Rab tethering model. Rabs recruit tethering factors, which in turn interact with SNARE proteins and activate the formation of SNARE complexes, leading to membrane fusion. Scale and stoichiometry are simplified for the illustration.

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