Activation of myosin Va function by melanophilin, a specific docking partner of myosin Va.
It is known that melanophilin is a myosin Va-targeting molecule that links myosin Va and the cargo vesicles in cells. Here we found that melanophilin directly activates the actin-activated ATPase activity of myosin Va and thus its motor activity. The actin-activated ATPase activity of the melanocyte-type myosin Va having exon-F was significantly activated by melanophilin by 4-fold. Although Rab27a binds to myosin Va/melanophilin complex, it did not affect the melanophilin-induced activation of myosin Va. Deletion of the C-terminal actin binding domain and N-terminal Rab binding domain of melanophilin resulted in no change in the activation of the ATPase by melanophilin, indicating that the myosin Va binding domain (MBD) is sufficient for the activation of myosin Va. Among MBDs, the interaction of MBD-2 with exon-F of myosin Va is critical for the binding of myosin Va and melanophilin, whereas MBD-1 interacting with the globular tail of myosin Va plays a more significant role in the activation of myosin Va ATPase activity. This is the first demonstration that the binding of the cargo molecule directly activates myosin motor activity. The present finding raises the idea that myosin motors are switched upon their binding to the cargo molecules, thus avoiding the waste of ATP consumption.
Li
Xiang-Dong
XD
Department of Physiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Ikebe
Reiko
R
Ikebe
Mitsuo
M
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D018995:Myosin Heavy Chains / Q000378:metabolism* / Q000502:physiology; D024701:Myosin Type V / Q000378:metabolism* / Q000502:physiology; D017434:Protein Structure, Tertiary; D011817:Rabbits
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C435724:Mlph protein, mouse; C513082:Myo5a protein, mouse; D024701:Myosin Type V; D018995:Myosin Heavy Chains