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.
|Number of pages||10|
|Journal||Molecular Genetics and Metabolism|
|State||Published - Sep 1999|
Bibliographical noteFunding Information:
This work was partially supported by shared resources of the Roswell Park Cancer Center Support Grant (P30 CA16056) and by NIH Grants HL51480, HL31698, and EY12104 (R.T.S.), DE09655 (D.C.), and HL56652 (S.W.W.). R.J.H. gratefully acknowledges the support of the Heart and Stroke Foundation of Ontario (Grant T-3373) and the Medical Research Council of Canada (Grant MT-5626). We thank Lijie Zhen for excellent technical assistance and Rosemary Elliott for assistance with analysis of the Snap23 mapping data.
- Hermansky-Pudlak syndrome
- Vesicular trafficking
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Molecular Biology