Rab27b Association with Melanosomes: Dominant Negative Mutants Disrupt Melanosomal Movement
| Autor: | Tung-Tien Sun, Preminda Samaraweera, Yanru Chen, Seth J. Orlow, Gert Kreibich |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Gene Expression
melanosome GTPase Dermatology Melanocyte Biology Biochemistry rab27 GTP-Binding Proteins GTP Phosphohydrolases Melanin Mice 03 medical and health sciences 0302 clinical medicine Myosin medicine Animals Point Mutation RNA Messenger Griscelli syndrome Molecular Biology Cells Cultured Actin 030304 developmental biology Melanosome Cell Nucleus Genetics 0303 health sciences Melanosomes Biological Transport Dendrites Cell Biology medicine.disease Rab melanin Cell biology Mice Inbred C57BL medicine.anatomical_structure rab GTP-Binding Proteins 030220 oncology & carcinogenesis Mutagenesis Site-Directed Melanocytes Guanosine Triphosphate myosin Va |
| Zdroj: | Journal of Investigative Dermatology. 118(6):933-940 |
| ISSN: | 0022-202X |
| DOI: | 10.1046/j.1523-1747.2002.01754.x |
| Popis: | The movement of melanosomes from post-Golgi compartments to the periphery of melanocytes is known to be regulated by factors including myosin Va and at least one Rab protein, Rab27a. Mutations in the genes encoding either protein in the mouse result in a hypopigmented phenotype mimicking the human disease Griscelli syndrome. Rab27b and Rab27a share 72% identity and they belong to the same melanocyte/platelet subfamily of Rab proteins. Rab27a orchestrates the transport of melanosomes by recruitment of the actin motor, myosin Va, onto melanosomes. By contrast, the function of Rab27b has remained elusive. In this study, we found that Rab27b mRNA is present in melanocytes and demonstrated the intrinsic GTPase activity of Rab27b protein. We explored the function of Rab27b by overexpression of two dominant negative mutants as well as the wild-type Rab27b in melan-a melanocytes. Green-fluorescent-protein-tagged Rab27b colocalizes with the melanosome marker tyrosinase-related protein 1 and with myosin Va at the cell periphery, whereas Rab27b mutants do not decorate melanosomes, and melanosomes in these mutant transfected cells redistribute from cell periphery to the perinuclear region. Furthermore, transient overexpression of the dominant negative forms of Rab27b caused diminution in both numbers and length of dendrites of melan-a cells. Our results suggest that Rab27b may regulate the outward movement of melanosomes and the formation or maintenance of dendritic extensions in melanocytes. |
| Databáze: | OpenAIRE |
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