Reduced pigmentation (rp), a mouse model of Hermansky-Pudlak syndrome, encodes a novel component of the BLOC-1 complex.
Document Type
Article
Publication Date
2004
Keywords
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
First Page
3181
Last Page
3189
JAX Source
Blood 2004 Nov; 104(10):3181-9.
Abstract
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.
Recommended Citation
Gwynn B,
Martina JA,
Bonifacino JS,
Sviderskaya EV,
Lamoreux ML,
Bennett DC,
Moriyama K,
Huizing M,
Helip WA,
Gahl WA,
Webb LS,
Lambert AJ,
Peters LL.
Reduced pigmentation (rp), a mouse model of Hermansky-Pudlak syndrome, encodes a novel component of the BLOC-1 complex. Blood 2004 Nov; 104(10):3181-9.