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Blood, 15 November 2004, Vol. 104, No. 10, pp. 3181-3189. Prepublished online as a Blood First Edition Paper on July 20, 2004; DOI 10.1182/blood-2004-04-1538. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-04-1538v1 104/10/3181    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gwynn, B. Articles by Peters, L. L. Search for Related Content PubMed PubMed Citation Articles by Gwynn, B. Articles by Peters, L. L. Related Collections Hemostasis, Thrombosis, and Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Reduced pigmentation (rp), a mouse model of Hermansky-Pudlak syndrome, encodes a novel component of the BLOC-1 complex Babette Gwynn, Jose A. Martina, Juan S. Bonifacino, Elena V. Sviderskaya, M. Lynn Lamoreux, Dorothy C. Bennett, Kengo Moriyama, Marjan Huizing, Amanda Helip-Wooley, William A. Gahl, Lisa S. Webb, Amy J. Lambert, and Luanne L. Peters From the Jackson Laboratory, Bar Harbor, ME; Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD; Department of Basic Medical Sciences, St George's Hospital Medical School, London, United Kingdom; College of Veterinary Medicine, Texas A&M University, College Station, TX; Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD. 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: The light side of platelet dense granules Richard T. Swank Blood 2004 104: 3006. [Full Text] [PDF] This article has been cited by other articles: S. R. G. Setty, D. Tenza, S. T. Truschel, E. Chou, E. V. Sviderskaya, A. C. Theos, M. L. Lamoreux, S. M. Di Pietro, M. Starcevic, D. C. Bennett, et al. BLOC-1 Is Required for Cargo-specific Sorting from Vacuolar Early Endosomes toward Lysosome-related Organelles Mol. Biol. Cell, March 1, 2007; 18(3): 768 - 780. [Abstract] [Full Text] [PDF] C. Wasmeier, M. Romao, L. Plowright, D. C. Bennett, G. Raposo, and M. C. Seabra Rab38 and Rab32 control post-Golgi trafficking of melanogenic enzymes J. Cell Biol., October 23, 2006; 175(2): 271 - 281. [Abstract] [Full Text] [PDF] S. Pulipparacharuvil, M. A. Akbar, S. Ray, E. A. Sevrioukov, A. S. Haberman, J. Rohrer, and H. Kramer Drosophila Vps16A is required for trafficking to lysosomes and biogenesis of pigment granules J. Cell Sci., August 15, 2005; 118(16): 3663 - 3673. [Abstract] [Full Text] [PDF] S. Chintala, W. Li, M. L. Lamoreux, S. Ito, K. Wakamatsu, E. V. Sviderskaya, D. C. Bennett, Y.-M. Park, W. A. Gahl, M. Huizing, et al. Slc7a11 gene controls production of pheomelanin pigment and proliferation of cultured cells PNAS, August 2, 2005; 102(31): 10964 - 10969. [Abstract] [Full Text] [PDF]

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