The Emerging Role of Rab5 in Membrane Receptor Trafficking and Signaling Pathways

Table 1

Summary of Rab5 regulator and effectors.

			Key structures	Functions	References
Regulators	GEFs	Rabex-5	Ubiquitin-binding domain, E3 ubiquitin ligase domain	Activation of Rab5 GTPases during endocytosis	[18]
		RME-6	Vps9-domain	Regulation of clathrin-coated vesicle uncoating and delivery of endocytic cargo to early endosomes	[19, 20]
		RIN1	Proline-rich domain, tyrosine 36	Internalization, trafficking and degradation of activated receptors, cytoskeleton remodeling	[21]
		p85	C-terminal and N-terminal domains	Activation of Rab5 GTPases during endocytosis, migration of cancer cells	[22–24]
	GAPs	Rab-GAP5	Tre2/Bub2/Cdc16 domain	Inactivation of Rab5 GTPases during endocytosis and trafficking	[25]
		Tuberin	C-terminal domain	Inactivation of Rab5 GTPases during endocytosis and trafficking	[26]
		Armus/TBC-2	PH domain	Inactivation of Rab5 to promote Rab5 to Rab7 conversion during endosome maturation	[27]
Effectors		EEA1	C-terminal and N-terminal domains, C2H2 zinc finger domain	Fusion, docking and sorting of the early endosome	[28, 29]
		Rabaptin-5	C-terminal domain	Fusion, docking and sorting of the early endosome	[30, 31]
		Rabenosyn-5	N-terminal domain, C2H2 zinc finger domain, and FYVE finger domain	Regulation of macropinocytosis, initiation of tubular endocytosis and surface flattening	[32, 33]
		APPL1/2	PH domain, PTB domain, and leucine zipper motif	Stable cargo-sorting compartments, membrane traffic/signaling, cell proliferation	[33, 34]
		ZFYVE21	FYVE-finger domain	Phosphoinositide remodeling of early endosome membranes to mediate signal activation and tissue inflammation	[35]
		Rabankyrin-5	FYVE finger domain, ankyrin repeats	Formation of endosomes and remodeling of the apical plasma membrane	[36]