title: Analyses of proteins involved in vesicular trafficking in platelets of mouse models of Hermansky Pudlak syndrome.
abstract: Hermansky Pudlak syndrome (HPS) is an autosomal recessive inherited disorder characterized by defects in synthesis and/or secretion of three related subcellular organelles: melanosomes, platelet-dense granules, and lysosomes. In the mouse, mutant forms of any of 14 separate genes result in an HPS-like phenotype. The mouse pearl and mocha genes encode subunits of the AP3 adaptor protein complex, confirming that HPS mutations involve proteins regulating intracellular vesicular trafficking. Therefore, expression of several additional proteins involved in vesicular transport was examined by immunoblotting of platelet extracts from HPS mutant and control mice. Platelet levels of SCAMPS (secretory carrier membrane proteins), Rab11, Rab31, NSF (N-ethylmaleimide-sensitive fusion protein), syntaxin 2, syntaxin 4, munc18c, and p115/TAP (p115/transcytosis-associated protein) were not significantly altered in several different HPS mutants. However, gunmetal (gm/gm) platelets contained decreased amounts of SNAP-23. The Snap23 gene was mapped to mouse chromosome 5, demonstrating it cannot encode the gm gene, which maps to chromosome 14. It is likely therefore that the gm gene functions upstream of SNAP-23 in vesicular trafficking.
authors.affiliation: Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors.forename: B
authors.initials: B
authors.lastname: Richards-Smith
authors.forename: E K
authors.initials: EK
authors.lastname: Novak
authors.forename: E K
authors.initials: EK
authors.lastname: Jang
authors.forename: P
authors.initials: P
authors.lastname: He
authors.forename: R J
authors.initials: RJ
authors.lastname: Haslam
authors.forename: D
authors.initials: D
authors.lastname: Castle
authors.forename: S W
authors.initials: SW
authors.lastname: Whiteheart
authors.forename: R T
authors.initials: RT
authors.lastname: Swank
mesh_terms: D016115:Albinism, Oculocutaneous / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001692:Biological Transport; D001792:Blood Platelets / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002874:Chromosome Mapping; D003594:Cytoplasmic Granules / Q000378:metabolism*; D004195:Disease Models, Animal; D019204:GTP-Binding Proteins / Q000378:metabolism; D000077614:Golgi Matrix Proteins; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D051938:Munc18 Proteins; D009115:Muridae; D052066:N-Ethylmaleimide-Sensitive Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D011506:Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D050765:Qa-SNARE Proteins; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins
chemical_list: D000954:Antigens, Surface; D002352:Carrier Proteins; D019204:GTP-Binding Proteins; D000077614:Golgi Matrix Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051938:Munc18 Proteins; D052066:N-Ethylmaleimide-Sensitive Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D011506:Proteins; D050765:Qa-SNARE Proteins; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C100493:SNAP23 protein, human; C083429:Scamp1 protein, rat; C107017:Snap23 protein, mouse; C497943:Stxbp3 protein, mouse; C091580:vesicular transport factor p115; C498733:Nsf protein, mouse; C498737:Nsf protein, rat