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Titolo:
Molecular characterization of the protein encoded by the Hermansky-Pudlak syndrome type 1 gene
Autore:
DellAngelica, EC; Aguilar, RC; Wolins, N; Hazelwood, S; Gahl, WA; Bonifacino, JS;
Indirizzi:
NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA NICHD Bethesda MD USA 20892 l & Metab Branch, NIH, Bethesda, MD 20892 USA NICHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA NICHD Bethesda MD USA 20892 Disorders Branch, NIH, Bethesda, MD 20892 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 2, volume: 275, anno: 2000,
pagine: 1300 - 1306
SICI:
0021-9258(20000114)275:2<1300:MCOTPE>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
AP-3 ADAPTER COMPLEX; PALE EAR EP; VESICLE FORMATION; LOCUS HETEROGENEITY; HPS GENE; CLATHRIN; ENDOCYTOSIS; MUTATION; TRANSPORT; DOMAIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Bonifacino, JS NICHD, Cell Biol & Metab Branch, NIH, Bldg 18T,Rm 101, Bethesda, MD 20892 USA NICHD Bldg 18T,Rm 101 Bethesda MD USA 20892 a, MD 20892 USA
Citazione:
E.C. Dell'Angelica et al., "Molecular characterization of the protein encoded by the Hermansky-Pudlak syndrome type 1 gene", J BIOL CHEM, 275(2), 2000, pp. 1300-1306

Abstract

Hermansky-Pudlak syndrome (HPS) comprises a group of genetic disorders characterized by defective lysosome-related organelles. The most common form of HPS (HPS type 1) is caused by mutations in a gene encoding a protein withno homology to any other known protein. Here we report the identification and biochemical characterization of this gene product, termed HPS1p, Endogenous HPS1p was detected in a wide variety of human cell lines and exhibitedan electrophoretic mobility corresponding to a protein of similar to 80 kDa, In contrast to previous theoretical analysis predicting that HPS1p is anintegral membrane protein, we found that this protein was predominantly cytosolic, with a small amount being peripherally associated with membranes, The sedimentation coefficient of the soluble form of HPS1p was similar to 6S as inferred from ultracentrifugation on sucrose gradients. HPS1p-deficient cells derived from patients with HPS type 1 displayed normal distribution and trafficking of the lysosomal membrane proteins, CD63 and Lamp-1. Thiswas in contrast to cells from HPS type 2 patients, having mutations in thebeta 3A subunit of the AP-3 adaptor complex, which exhibited increased routing of these lysosomal proteins through the plasma membrane, Similar analyses performed on fibroblasts from 10 different mouse models of HPS revealedthat only the AP-3 mutants pearl and mocha display increased trafficking of Lamp-1 through the plasma membrane. Taken together, these observations suggest that the product of the HPS1 gene is a cytosolic protein capable of associating with membranes and involved in the biogenesis and/or function oflysosome-related organelles by a mechanism distinct from that dependent onthe AP-3 complex.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/09/20 alle ore 13:22:15