RAB5A

Endocytosis of cell surface receptors plays an important role in regulating cell signaling cascades. In some cases, internalization of an activated receptor attenuates the signaling process, while in other cases the clustering of activated receptors on early endosomal structures has been proposed to be essential for fully activating signaling cascades.

Regulating the movement of receptors and other signaling proteins through the endocytic pathway, therefore, has a direct impact on cellular homeostasis.

The small GTPase RAB5A is a crucial regulatory component of the endocytic pathway. Activation of RAB5A is mediated by GDP-GTP exchange factors (GEFs) that generate the Rab5-GTP complex.

A large number of proteins have been identified that contain a specific, highly conserved domain (Vps9) that catalyzes nucleotide exchange on Rab5, linking the regulation of cell signaling cascades with intracellular receptor trafficking through the endocytic pathway.

Function

 regulatory factor in the early endocytic pathway
 endosomal compartment
 endocytic membrane fusion
 modulating endocytosis
 remodeling of endosomes during lysosome biogenesis (12571288)

References

 Carney DS, Davies BA, Horazdovsky BF. Vps9 domain-containing proteins: activators of Rab5 GTPases from yeast to neurons. Trends Cell Biol. 2006 Jan;16(1):27-35. PMID: 16330212