| Autor: |
Gahl William A, Boissy Raymond E, Mommaas Mieke, Dorward Heidi, Westbroek Wendy, Helip-Wooley Amanda, Huizing Marjan |
| Jazyk: |
angličtina |
| Rok vydání: |
2005 |
| Předmět: |
|
| Zdroj: |
BMC Cell Biology, Vol 6, Iss 1, p 33 (2005) |
| Druh dokumentu: |
article |
| ISSN: |
1471-2121 |
| DOI: |
10.1186/1471-2121-6-33 |
| Popis: |
Abstract Background Hermansky-Pudlak syndrome (HPS) is a disorder of lysosome-related organelle biogenesis characterized by oculocutaneous albinism and prolonged bleeding. These clinical findings reflect defects in the formation of melanosomes in melanocytes and dense bodies in platelets. HPS type-3 (HPS-3) results from mutations in the HPS3 gene, which encodes a 1004 amino acid protein of unknown function that contains a predicted clathrin-binding motif (LLDFE) at residues 172–176. Results Clathrin was co-immunoprecipitated by HPS3 antibodies from normal but not HPS3 null melanocytes. Normal melanocytes expressing a GFP-HPS3 fusion protein demonstrated partial co-localization of GFP-HPS3 with clathrin following a 20°C temperature block. GFP-HPS3 in which the predicted clathrin-binding domain of HPS3 was mutated (GFP-HPS3-delCBD) did not co-localize with clathrin under the same conditions. Immunoelectron microscopy of normal melanocytes expressing GFP-HPS3 showed co-localization of GFP-HPS3 with clathrin, predominantly on small vesicles in the perinuclear region. In contrast, GFP-HPS3-delCBD did not co-localize with clathrin and exhibited a largely cytoplasmic distribution. Conclusion HPS3 associates with clathrin, predominantly on small clathrin-containing vesicles in the perinuclear region. This association most likely occurs directly via a functional clathrin-binding domain in HPS3. These results suggest a role for HPS3 and its protein complex, BLOC-2, in vesicle formation and trafficking. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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