Reduced pigmentation (rp), a mouse model of Hermansky-Pudlak syndrome, encodes a novel component of the BLOC-1 complex.
Animals, Carrier-Proteins, Cell-Line-Tumor, Chromosome-Mapping, Cloning-Molecular, Disease-Models-Animal, Female, Fibroblasts, Hermanski-Pudlak-Syndrome, Humans, Lysosomes, Melanocytes, Melanoma, Mice-Inbred-C57BL, Mice-Mutant-Strains, Molecular-Sequence-Data, Phenotype, Pigmentation, Transcription-Factors
Blood 2004 Nov; 104(10):3181-9.
Hermansky-Pudlak syndrome (HPS), a disorder of organelle biogenesis, affects lysosomes, melanosomes, and platelet dense bodies. Seven genes cause HPS in humans (HPS1-HPS7) and at least 15 nonallelic mutations cause HPS in mice. Where their function is known, the HPS proteins participate in protein trafficking and vesicle docking/fusion events during organelle biogenesis. HPS-associated genes participate in at least 4 distinct protein complexes: the adaptor complex AP-3; biogenesis of lysosome-related organelles complex 1 (BLOC-1), consisting of 4 HPS proteins (pallidin, muted, cappuccino, HPS7/sandy); BLOC-2, consisting of HPS6/ruby-eye, HPS5/ruby-eye-2, and HPS3/cocoa; and BLOC-3, consisting of HPS1/pale ear and HPS4/light ear. Here, we report the cloning of the mouse HPS mutation reduced pigmentation (rp). We show that the wild-type rp gene encodes a novel, widely expressed 195-amino acid protein that shares 87% amino acid identity with its human orthologue and localizes to punctate cytoplasmic structures. Further, we show that phosphorylated RP is part of the BLOC-1 complex. In mutant rp/rp mice, a premature stop codon truncates the protein after 79 amino acids. Defects in all the 5 known components of BLOC-1, including RP, cause severe HPS in mice, suggesting that the subunits are nonredundant and that BLOC-1 plays a key role in organelle biogenesis.
Gwynn, B; Martina, J A.; Bonifacino, J S.; Sviderskaya, E V.; Lamoreux, M L.; Bennett, D C.; Moriyama, K; Huizing, M; Helip, Wooley A.; Gahl, W A.; Webb, L S.; Lambert, A J.; and Peters, L L., "Reduced pigmentation (rp), a mouse model of Hermansky-Pudlak syndrome, encodes a novel component of the BLOC-1 complex." (2004). Faculty Research 2000 - 2009. 990.
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