title: Insights into the biogenesis of lysosome-related organelles from the study of the Hermansky-Pudlak syndrome.
abstract: Lysosome-related organelles (LROs) are a family of cell-type-specific organelles that include melanosomes, platelet dense bodies, and cytotoxic T cell granules. The name, LRO, recognizes the fact that all of these organelles contain subsets of lysosomal proteins in addition to cell-type-specific proteins. The recent identification of genetic disorders that cause combined defects in several of these organelles indicates that they share common biogenetic pathways. Studies of one of these disorders, the Hermansky-Pudlak syndrome (HPS), have provided helpful insights into the molecular machinery involved in LRO biogenesis. HPS is a genetically heterogeneous disorder caused by mutations in any of 7 genes in humans and 15 genes in mice. These genes encode subunits of 4 multi-protein complexes named AP-3, BLOC-1, BLOC-2 and BLOC-3, in addition to miscellaneous components of the general protein trafficking machinery. The AP-3 complex is a coat protein involved in vesicle formation and cargo selection in the endosomal-lysosomal system. One of these cargo molecules is the melanosomal enzyme, tyrosinase, the missorting of which may explain the defective melanosomes in AP-3-deficient humans and mice. The function of the BLOC complexes is unknown, although they are thought to mediate either vesicle tethering/fusion or cytoplasmic dispersal of LROs. Further studies of these complexes should contribute to the elucidation of the mechanisms of LRO biogenesis and the pathogenesis of HPS.
authors.affiliation: Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Building 18T/Room 101, National Institutes of Health, Bethesda, MD 20892, USA. juan@helix.nih.gov
authors.forename: Juan S
authors.initials: JS
authors.lastname: Bonifacino
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D011992:Endosomes / Q000378:metabolism; D022861:Hermanski-Pudlak Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism; D046912:Multiprotein Complexes; D015388:Organelles / Q000378:metabolism*; D021382:Protein Sorting Signals; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport
chemical_list: D046912:Multiprotein Complexes; D021382:Protein Sorting Signals; D021122:Protein Subunits; D014442:Monophenol Monooxygenase