Human Molecular Genetics, 2000, Vol. 9, No. 3 375-385
© 2000 Oxford University Press
The Hermansky–Pudlak syndrome (HPS) protein is part of a high molecular weight complex involved in biogenesis of early melanosomes
Human Medical Genetics Program, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, B-161, Denver, CO 80262, USA and 1Section Recherche, Institut Curie, Paris 75005, France
Hermansky–Pudlak syndrome (HPS) is a rare autosomal recessive disorder in which oculocutaneous albinism, bleeding tendency and a ceroid-lipofuscin lysosomal storage disease result from defects of multiple cytoplasmic organelles: melanosomes, platelet dense granules and lysosomes. The HPS polypeptide, a 700 amino acid protein which is unrelated to any known proteins, is likely to be involved in the biogenesis of these different organelles. Here, we show that HPS is a non-glycosylated, non-membrane protein which is a component of two distinct high molecular weight complexes. In non-melanotic cells the HPS protein is contained almost entirely in an ~200 kDa complex that is widely distributed throughout the cytosol. In melanotic cells the HPS protein is partitioned between this cytosolic complex and a >500 kDa complex that appears to consist of the ~200 kDa complex in association with membranous components. Subcellular fractionation, immunofluorescence and immunoelectron microscopy studies indicate that the membrane-associated HPS complex of melanotic cells is associated with tubulovesicular structures, small non-coated vesicles, and nascent and early-stage melanosomes. These findings suggest that the HPS complex is involved in the biogenesis of early melanosomes.
+ These authors contributed equally to this work
§ Present address: Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
¶ Present address: Cereon Genomics, LLC, Cambridge, MA 02139, USA
To whom correspondence should be addressed. Tel: +1 303 315 0409; Fax: +1 303 315 0407; Email: richard.spritz@uchsc.edu
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