The melanosome as a model to study organelle motility in mammals.
Melanosomes are lysosome-related organelles within which melanin pigment is synthesized. The molecular motors that allow these organelles to move within melanocytes have been the subject of intense study in several organisms. In mammals, melanosomes travel bi-directionally along microtubule tracks. The anterograde movement, i.e., towards microtubule plus-ends at the periphery, is accomplished by proteins of the kinesin superfamily, whereas the retrograde movement, i.e., towards microtubule minus-ends at the cell center, is achieved by dynein and dynein-associated proteins. At the periphery, melanosomes interact with the actin cytoskeleton via a tripartite complex formed by the small GTPase Rab27a, melanophilin and myosin Va, an actin-based motor. This interaction is essential for the maintenance of a dispersed state of the melanosomes, as shown by the perinuclear clustering of organelles in mutants in any of the referred proteins. In the retinal pigment epithelium, a similar complex formed by Rab27a, a melanophilin homolog called MyRIP and myosin VIIa is probably responsible for the tethering of melanosomes to the actin cytoskeleton. The coordination of motor activities is still poorly characterized, although some models have emerged in recent years and are discussed here. Unraveling regulatory mechanisms responsible for melanosome motility in pigmented cells will provide general insights into organelles dynamics within eukaryotic cells.
Barral
Duarte C
DC
Division of Biomedical Sciences, Faculty of Medicine, Imperial College London, London, UK.
Seabra
Miguel C
MC
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002465:Cell Movement; D003599:Cytoskeleton / Q000378:metabolism; D004398:Dyneins / Q000378:metabolism; D006801:Humans; D016547:Kinesins / Q000378:metabolism; D008322:Mammals / Q000502:physiology; D008544:Melanocytes / Q000502:physiology; D020460:Melanosomes / Q000378:metabolism / Q000473:pathology*; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D018995:Myosin Heavy Chains / Q000378:metabolism; D024701:Myosin Type V / Q000378:metabolism; D011485:Protein Binding; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000075745:rab27 GTP-Binding Proteins
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C492410:MLPH protein, human; D000075745:rab27 GTP-Binding Proteins; C077511:MYO5A protein, human; D024701:Myosin Type V; C066694:RAB27A protein, human; D018995:Myosin Heavy Chains; D004398:Dyneins; D016547:Kinesins; D020691:rab GTP-Binding Proteins