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Rab27a enables myosin Va-dependent melanosome capture by recruiting the myosin to the organelle. Paper-8762782. Genetic evidence suggests that Rab27a, the product of the ashen locus, functions with myosin Va in this process. Paper-8762782.
Conversely, introduction into wild-type melanocytes of the GDP-bound version of Rab27a generates an ashen/dilute phenotype. Paper-8762782.
This phenotype suggests that ashen melanocytes, like dilute melanocytes, are defective in peripheral melanosome capture.
These results argue that Rab27a serves as a myosin Va 'receptor', and add to the growing evidence that Rab GTPases regulate vesicle motors as well as SNARE pairing. Paper-8762782.
We suggest that Rab27a, in its GTP-bound and melanosome-associated form, predominates in the periphery, and that it is this form that recruits the myosin, enabling capture. Paper-8762782.
Rab27a colocalizes with end-stage melanosomes in wild-type cells, and is most concentrated in melanosome-rich dendritic tips, where it also colocalizes with myosin Va. Paper-8762782.
Consistent with this, introduction into ashen melanocytes of cDNAs encoding wild-type and GTP-bound versions of Rab27a restores the peripheral accumulation of melanosomes in a microtubule-dependent manner. Paper-8762782.
Finally, neither endogenous myosin Va nor an expressed, GFP-tagged, myosin Va tail domain fusion protein colocalize with melanosomes in ashen melanocytes, in contrast to that seen previously in wild-type cells. Paper-8762782.
These results argue that Rab27a serves to enable the myosinVa-dependent capture of melanosomes delivered to the periphery by bidirectional, microtubule-dependent transport, and that it does so by recruiting the myosin to the melanosome surface. Paper-8762782.
The peripheral accumulation of melanosomes characteristic of wild-type mouse melanocytes is driven by a cooperative process involving long-range, bidirectional, microtubule-dependent movements coupled to capture and local movement in the actin-rich periphery by myosin Va, the product of the dilute locus. Paper-8762782.
Here we show that ashen melanocytes, like dilute melanocytes, exhibit normal dendritic morphology and melanosome biogenesis, an abnormal accumulation of end-stage melanosomes in the cell center, and rapid, bidirectional, microtubule-dependent melanosome movements between the cell center and the periphery.
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