PMID:11452004

Citation	Huizing, M, Sarangarajan, R, Strovel, E, Zhao, Y, Gahl, WA and Boissy, RE (2001) AP-3 mediates tyrosinase but not TRP-1 trafficking in human melanocytes. Mol. Biol. Cell 12:2075-85
Abstract	Patients with Hermansky-Pudlak syndrome type 2 (HPS-2) have mutations in the beta 3A subunit of adaptor complex-3 (AP-3) and functional deficiency of this complex. AP-3 serves as a coat protein in the formation of new vesicles, including, apparently, the platelet's dense body and the melanocyte's melanosome. We used HPS-2 melanocytes in culture to determine the role of AP-3 in the trafficking of the melanogenic proteins tyrosinase and tyrosinase-related protein-1 (TRP-1). TRP-1 displayed a typical melanosomal pattern in both normal and HPS-2 melanocytes. In contrast, tyrosinase exhibited a melanosomal (i.e., perinuclear and dendritic) pattern in normal cells but only a perinuclear pattern in the HPS-2 melanocytes. In addition, tyrosinase exhibited a normal pattern of expression in HPS-2 melanocytes transfected with a cDNA encoding the beta 3A subunit of the AP-3 complex. This suggests a role for AP-3 in the normal trafficking of tyrosinase to premelanosomes, consistent with the presence of a dileucine recognition signal in the C-terminal portion of the tyrosinase molecule. In the AP-3-deficient cells, tyrosinase was also present in structures resembling late endosomes or multivesicular bodies; these vesicles contained exvaginations devoid of tyrosinase. This suggests that, under normal circumstances, AP-3 may act on multivesicular bodies to form tyrosinase-containing vesicles destined to fuse with premelanosomes. Finally, our studies demonstrate that tyrosinase and TRP-1 use different mechanisms to reach their premelanosomal destination.
Links	PubMed PMC55657
Keywords	Adaptor Proteins, Vesicular Transport; Antigens, CD/metabolism; Antigens, CD63; Biological Transport; Carrier Proteins/genetics; Carrier Proteins/metabolism; Carrier Proteins/physiology; Cell Line; Hermanski-Pudlak Syndrome/metabolism; Humans; Melanocytes/metabolism; Membrane Glycoproteins; Membrane Proteins/genetics; Membrane Proteins/metabolism; Membrane Proteins/physiology; Monomeric Clathrin Assembly Proteins; Monophenol Monooxygenase/metabolism; Oxidoreductases; Platelet Membrane Glycoproteins/metabolism; Proteins/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:AP3B1	involved_in	GO:0032438: melanosome organization	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:AP3B1		GO:0032438: melanosome organization	ECO:0000315:		P		In Fig. 5, normal melanosomes stain for tyrosinase. HPS-2 (AP-3 beta mutant) melanosomes lack tyrosinase.	complete CACAO 2450

References

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