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Prepublished online as a Blood First Edition Paper on February 6, 2003; DOI 10.1182/blood-2003-01-0020. This Article Full Text (PDF) All Versions of this Article: 2003-01-0020v1 101/11/4402    most recent Alert me when this article is cited Alert me if a correction is posted 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 Ciciotte, S. L Articles by Peters, L. L Search for Related Content PubMed PubMed Citation Articles by Ciciotte, S. L Articles by Peters, L. L Related Collections Related Article in Blood Online Social Bookmarking                   What's this? Submitted January 3, 2003 Accepted January 21, 2003 Cappuccino, a mouse model of Hermansky-Pudlak syndrome, encodes a novel protein that is part of the pallidin-muted complex (BLOC-1) Steven L Ciciotte, Babette Gwynn, Kengo Moriyama, Marjan Huizing, William A Gahl, Juan S Bonifacino, and Luanne L Peters* The Jackson Laboratory, Bar Harbor, ME, USA Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA * Corresponding author; email: luanne{at}jax.org. Hermansky-Pudlak syndrome (HPS) is a disorder of organelle biogenesis affecting three related organelles--melanosomes, platelet dense bodies, and lysosomes. Four genes causing HPS in humans (HPS1-HPS4) are known, and at least fifteen non-allelic mutations cause HPS in the mouse. Where their functions are known, the HPS-associated proteins are involved in some aspect of intracellular vesicular trafficking, i.e., protein sorting and vesicle docking and fusion. Biochemical and genetic evidence indicates that the HPS-associated genes encode components of at least three distinct protein complexes: the adaptor complex AP-3; the HPS1/HPS4 complex; and BLOC-1 (biogenesis of lysosome-related organelles complex-1), consisting of the proteins encoded at two mouse HPS loci, pallid (pa) and muted (mu), and at least three other unidentified proteins. Here, we report the cloning of the mouse HPS mutation cappuccino (cno). We show that the wildtype cno gene encodes a novel, ubiquitously expressed cytoplasmic protein that co-assembles with pallidin and the muted protein in the BLOC-1 complex. Further, we identify a frameshift mutation in mutant cno/cno mice. The C-terminal 81 AAs are replaced with 72 different AAs in the mutant CNO protein, and its ability to interact in BLOC-1 is abolished. We performed mutation screening of human HPS patients and failed to identify any CNO defects. Notably, while defects in components of the HPS1/HPS4 and the AP-3 complexes are associated with HPS in humans, no defects in the known components of BLOC-1 have been identified in 142 HPS patients screened to date, suggesting that BLOC-1 function may be critical in man. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Novel genes for specialized organelles Richard T. Swank Blood 2003 101: 4229. [Full Text] [PDF] This article has been cited by other articles: P. V. Ryder and V. Faundez Schizophrenia: The "BLOC" May Be in the Endosomes Sci. Signal., October 20, 2009; 2(93): pe66 - pe66. [Abstract] [Full Text] [PDF] K. Newell-Litwa, G. Salazar, Y. Smith, and V. 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J. Pathol., January 1, 2005; 166(1): 231 - 240. [Abstract] [Full Text] [PDF] B. Gwynn, J. A. Martina, J. S. Bonifacino, E. V. Sviderskaya, M. L. Lamoreux, D. C. Bennett, K. Moriyama, M. Huizing, A. Helip-Wooley, W. A. Gahl, et al. Reduced pigmentation (rp), a mouse model of Hermansky-Pudlak syndrome, encodes a novel component of the BLOC-1 complex Blood, November 15, 2004; 104(10): 3181 - 3189. [Abstract] [Full Text] [PDF] M. Starcevic and E. C. Dell'Angelica Identification of Snapin and Three Novel Proteins (BLOS1, BLOS2, and BLOS3/Reduced Pigmentation) as Subunits of Biogenesis of Lysosome-related Organelles Complex-1 (BLOC-1) J. Biol. Chem., July 2, 2004; 279(27): 28393 - 28401. [Abstract] [Full Text] [PDF] R. Gautam, S. Chintala, W. Li, Q. Zhang, J. Tan, E. K. Novak, S. M. Di Pietro, E. C. Dell'Angelica, and R. T. Swank The Hermansky-Pudlak Syndrome 3 (Cocoa) Protein Is a Component of the Biogenesis of Lysosome-related Organelles Complex-2 (BLOC-2) J. Biol. Chem., March 26, 2004; 279(13): 12935 - 12942. [Abstract] [Full Text] [PDF] J. A. Martina, K. Moriyama, and J. S. Bonifacino BLOC-3, a Protein Complex Containing the Hermansky-Pudlak Syndrome Gene Products HPS1 and HPS4 J. Biol. Chem., August 1, 2003; 278(31): 29376 - 29384. [Abstract] [Full Text] [PDF]

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