title: Murine Hermansky-Pudlak syndrome genes: regulators of lysosome-related organelles.
abstract: In the mouse, at least 16 genes regulate vesicle trafficking to specialized lysosome-related organelles, including platelet dense granules and melanosomes. Fourteen of these genes have been identified by positional cloning. All 16 mouse mutants are models for the genetically heterogeneous human disease, Hermansky-Pudlak Syndrome (HPS). Five HPS genes encode known vesicle trafficking proteins. Nine genes are novel, are found only in higher eukaryotes and encode members of three protein complexes termed BLOCs (Biogenesis of Lysosome-related Organelles Complexes). Mutations in murine HPS genes, which encode protein co-members of BLOCs, produce essentially identical phenotypes. In addition to their well-known effects on pigmentation, platelet function and lysosome secretion, HPS genes control a wide range of physiological processes including immune recognition, neuronal functions and lung surfactant trafficking. Studies of the molecular functions of HPS proteins will reveal important details of vesicle trafficking and may lead to therapies for HPS.
authors.affiliation: Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Michael E
authors.initials: ME
authors.lastname: Rusiniak
authors.forename: Sreenivasulu
authors.initials: S
authors.lastname: Chintala
authors.forename: Rashi
authors.initials: R
authors.lastname: Gautam
authors.forename: Edward K
authors.initials: EK
authors.lastname: Novak
authors.forename: Richard T
authors.initials: RT
authors.lastname: Swank
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D003001:Cloning, Molecular; D004195:Disease Models, Animal; D022861:Hermanski-Pudlak Syndrome / Q000235:genetics*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D020460:Melanosomes / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008954:Models, Biological; D009154:Mutation; D015388:Organelles / Q000378:metabolism*