title: Hermansky-Pudlak syndrome: a disease of protein trafficking and organelle function.
abstract: The Hermansky-Pudlak syndrome (HPS) is a collection of related autosomal recessive disorders which are genetically heterogeneous. There are eight human HPS subtypes, characterized by oculocutaneous albinism and platelet storage disease; prolonged bleeding, congenital neutropenia, pulmonary fibrosis, and granulomatous colitis can also occur. HPS is caused primarily by defects in intracellular protein trafficking that result in the dysfunction of intracellular organelles known as lysosome-related organelles. HPS gene products are all ubiquitously expressed and all associate in various multi-protein complexes, yet HPS has cell type-specific disease expression. Impairment of specialized secretory cells such as melanocytes, platelets, lung alveolar type II epithelial cells and cytotoxic T cells are observed in HPS. This review summarizes recent molecular, biochemical and cell biological analyses together with clinical studies that have led to the correlation of molecular pathology with clinical manifestations and led to insights into such diverse disease processes such as albinism, fibrosis, hemorrhage, and congenital neutropenia.
authors.affiliation: Department of Dermatology, Veterans Affairs Medical Center 190, University of California, 4150 Clement St., San Francisco, USA. weim@derm.ucsf.edu
authors.forename: Maria L
authors.initials: ML
authors.lastname: Wei
mesh_terms: D033963:Adaptor Protein Complex 3; D033966:Adaptor Protein Complex beta Subunits; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D020662:Guanine Nucleotide Exchange Factors; D022861:Hermanski-Pudlak Syndrome / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D015388:Organelles / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C439973:AP3B1 protein, human; D033963:Adaptor Protein Complex 3; D033966:Adaptor Protein Complex beta Subunits; C509457:BLOC1S3 protein, human; D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D020662:Guanine Nucleotide Exchange Factors; C102160:HPS1 protein, human; C432680:HPS3 protein, human; C451752:HPS4 protein, human; C493900:HPS5 protein, human; C493901:HPS6 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D011506:Proteins