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Cappuccino, a mouse model of Hermansky-Pudlak syndrome, encodes a novel protein that is part of the pallidin-muted complex (BLOC-1).

Hermansky-Pudlak syndrome (HPS) is a disorder of organelle biogenesis affecting 3 related organelles-melanosomes, platelet dense bodies, and lysosomes. Four genes causing HPS in humans (HPS1-HPS4) are known, and at least 15 nonallelic mutations cause HPS in the mouse. Where their functions are known, the HPS-associated proteins are involved in some aspect of intracellular vesicular trafficking, that is, protein sorting and vesicle docking and fusion. Biochemical and genetic evidence indicates that the HPS-associated genes encode components of at least 3 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 2 mouse HPS loci, pallid (pa) and muted (mu), and at least 3 other unidentified proteins. Here, we report the cloning of the mouse HPS mutation cappuccino (cno). We show that the wild-type cno gene encodes a novel, ubiquitously expressed cytoplasmic protein that coassembles 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 amino acids are replaced with 72 different amino acids in the mutant CNO protein, and its ability to interact in BLOC-1 is abolished. We performed mutation screening of patients with HPS and failed to identify any CNO defects. Notably, although 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 patients with HPS screened to date, suggesting that BLOC-1 function may be critical in humans.

Pubmed ID: 12576321


  • Ciciotte SL
  • Gwynn B
  • Moriyama K
  • Huizing M
  • Gahl WA
  • Bonifacino JS
  • Peters LL



Publication Data

June 1, 2003

Associated Grants

  • Agency: NCI NIH HHS, Id: CA34196
  • Agency: NHLBI NIH HHS, Id: HL55321
  • Agency: NHLBI NIH HHS, Id: R01 HL055321
  • Agency: NCRR NIH HHS, Id: RR01183

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Carrier Proteins
  • DNA Mutational Analysis
  • Fibroblasts
  • Hermanski-Pudlak Syndrome
  • Humans
  • Lectins
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Protein Binding
  • Tissue Distribution
  • Vesicular Transport Proteins