Reactome | HPS1:HPS4 exchange GTP for GDP on RAB32 and RAB38

HPS1:HPS4 exchange GTP for GDP on RAB32 and RAB38

Stable Identifier

R-HSA-8877760

Type

Reaction [transition]

Species

Homo sapiens

Compartment

melanosome membrane, cytosol

ReviewStatus

5/5

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HPS1:HPS4 exchange GTP for GDP on RAB32 and RAB38

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RAB32 and RAB38 play non-redundant but overlapping roles in melanosome and lysosome-related organelle (LRO) biogenesis (Loftus et al, 2002; Wasmeier et al, 2006; Lopes et al, 2007; Wang et al, 2008; Bultema et al, 2012; reviewed in Bultema and di Pietro, 2012). Through interaction with effector protein ANKRD27 (also known as VARP, a RAB21-specific GEF), RAB32 and RAB38 control trafficking of melanogenic enzymes; ANKRD27 GEF activity does not appear to be essential for this, however (Tamura et al, 2009; Tamura et al, 2011; Ohbayahsi et al, 2012). BLOC-3, a dimeric complex of HPS1 and HPS4, has RAB32- and RAB38 GEF activity and mutation in the genes encoding HPS1 and HPS4 results in defects in pigmentation and mislocalization of RAB32 and 38, and are associated with the rare autosomal recessive disorder Hermansky-Pudlak Syndrome (Gerondopoulos et al, 2012; reviewed in Ishida et al, 2016). Interaction of RAB32:GDP or RAB38:GDP with BLOC-3 promotes release of GDP, allowing GTP to bind, and precludes the interaction of the RAB proteins with GDI and CHM proteins.

Literature References

PubMed ID	Title	Journal	Year
17043139	Rab38 and Rab32 control post-Golgi trafficking of melanogenic enzymes Seabra, MC, Bennett, DC, Plowright, L, Raposo, G, Romao, M, Wasmeier, C	J. Cell Biol.	2006
22171327	The Rab21-GEF activity of Varp, but not its Rab32/38 effector function, is required for dendrite formation in melanocytes Tamura, K, Fukuda, M, Yatsu, A, Ohbayashi, N	Mol. Biol. Cell	2012
17671165	Melanosome maturation defect in Rab38-deficient retinal pigment epithelium results in instability of immature melanosomes during transient melanogenesis Seabra, MC, Lopes, VS, Wasmeier, C, Futter, CE	Mol. Biol. Cell	2007
23084991	BLOC-3 mutated in Hermansky-Pudlak syndrome is a Rab32/38 guanine nucleotide exchange factor Linford, A, Barr, FA, Liang, JR, Gerondopoulos, A, Langemeyer, L	Curr. Biol.	2012
11917121	Mutation of melanosome protein RAB38 in chocolate mice Antonellis, A, Pavan, WJ, Loftus, SK, Wu, X, Larson, DM, Baxter, LL, Jiang, Y, Chen, Y, Bittner, M, Hammer, JA	Proc. Natl. Acad. Sci. U.S.A.	2002
22511774	BLOC-2, AP-3, and AP-1 proteins function in concert with Rab38 and Rab32 proteins to mediate protein trafficking to lysosome-related organelles Ambrosio, AL, Di Pietro, SM, Bultema, JJ, Burek, CL	J. Biol. Chem.	2012
21187289	Structure-function analysis of VPS9-ankyrin-repeat protein (Varp) in the trafficking of tyrosinase-related protein 1 in melanocytes Tamura, K, Fukuda, M, Ohbayashi, N, Ishibashi, K	J. Biol. Chem.	2011
23247405	Cell type-specific Rab32 and Rab38 cooperate with the ubiquitous lysosome biogenesis machinery to synthesize specialized lysosome-related organelles Di Pietro, SM, Bultema, JJ	Small GTPases	2013
19403694	Varp is a novel Rab32/38-binding protein that regulates Tyrp1 trafficking in melanocytes Tamura, K, Fukuda, M, Itoh, T, Ohbayashi, N, Kanno, E, Maruta, Y	Mol. Biol. Cell	2009
27246931	Multiple Types of Guanine Nucleotide Exchange Factors (GEFs) for Rab Small GTPases Oguchi, ME, Fukuda, M, Ishida, M	Cell Struct. Funct.	2016
18477474	Varp interacts with Rab38 and functions as its potential effector Ren, F, Zhai, Y, Zhang, X, Chang, Z, Wang, F, Zhang, X, Wang, Y, Zhang, H	Biochem. Biophys. Res. Commun.	2008