| http://purl.uniprot.org/citations/30837268 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30837268 | http://www.w3.org/2000/01/rdf-schema#comment | "HPS4 biogenesis of lysosome-related organelles complex 3 subunit 2 (HPS4) is one of the genes whose mutations have been associated with Hermansky-Pudlak syndrome (HPS), characterized by ocular albinism and susceptibility to bleeding because of defects in the biogenesis of lysosome-related organelles such as melanosomes. HPS4 protein forms a BLOC-3 complex with HPS1, another HPS gene product, and the complex has been proposed to function as a guanine nucleotide exchange factor (GEF) for RAB32, a member of the Rab small GTPase family (Rab32), and Rab38 (Rab32/38-GEF) and also as a Rab9 effector. Although both Rab32/38 and Rab9 have been shown previously to be involved in melanogenesis in mammalian epidermal melanocytes, the functional relationships of these small GTPases with BLOC-3 remain unknown. In this study, we used site-directed mutagenesis to generate HPS4 mutants that specifically lack either Rab32/38-GEF activity or Rab9-binding activity and investigated their involvement in melanogenesis of melan-le cells (an HPS4-deficient melanocyte cell line derived from light ear mice). Melan-le cells exhibit a clear hypopigmentation phenotype, i.e. reduced expression and abnormal distribution of tyrosinase and reduced melanin content. Although re-expression of WT HPS4 completely rescued this phenotype, the Rab32/38-GEF activity-deficient HPS4 mutant failed to restore melanin content and tyrosinase trafficking in these cells. Unexpectedly, as WT HPS4, the Rab9 binding-deficient HPS4 mutant completely rescued the phenotype. These results indicate that activation of Rab32/38 by HPS4 (or BLOC-3) is essential for melanogenesis of cultured melanocytes and that Rab9 likely regulates melanogenesis independently of HPS4."xsd:string |
| http://purl.uniprot.org/citations/30837268 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.ra119.007345"xsd:string |
| http://purl.uniprot.org/citations/30837268 | http://purl.uniprot.org/core/author | "Fukuda M."xsd:string |
| http://purl.uniprot.org/citations/30837268 | http://purl.uniprot.org/core/author | "Ishida M."xsd:string |
| http://purl.uniprot.org/citations/30837268 | http://purl.uniprot.org/core/author | "Marubashi S."xsd:string |
| http://purl.uniprot.org/citations/30837268 | http://purl.uniprot.org/core/author | "Kinoshita R."xsd:string |
| http://purl.uniprot.org/citations/30837268 | http://purl.uniprot.org/core/author | "Ohishi Y."xsd:string |
| http://purl.uniprot.org/citations/30837268 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/30837268 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/30837268 | http://purl.uniprot.org/core/pages | "6912-6922"xsd:string |
| http://purl.uniprot.org/citations/30837268 | http://purl.uniprot.org/core/title | "The BLOC-3 subunit HPS4 is required for activation of Rab32/38 GTPases in melanogenesis, but its Rab9 activity is dispensable for melanogenesis."xsd:string |
| http://purl.uniprot.org/citations/30837268 | http://purl.uniprot.org/core/volume | "294"xsd:string |
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