Activation of myosin Va function by melanophilin, a specific docking partner of myosin Va

被引:79
作者
Li, XD [1 ]
Ikebe, R [1 ]
Ikebe, M [1 ]
机构
[1] Univ Massachusetts, Sch Med, Dept Physiol, Worcester, MA 01655 USA
关键词
D O I
10.1074/jbc.M413295200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:17815 / 17822
页数:8
相关论文
共 32 条
[1]   A millennial myosin census [J].
Berg, JS ;
Powell, BC ;
Cheney, RE .
MOLECULAR BIOLOGY OF THE CELL, 2001, 12 (04) :780-794
[2]   BRAIN MYOSIN-V IS A 2-HEADED UNCONVENTIONAL MYOSIN WITH MOTOR-ACTIVITY [J].
CHENEY, RE ;
OSHEA, MK ;
HEUSER, JE ;
COELHO, MV ;
WOLENSKI, JS ;
ESPREAFICO, EM ;
FORSCHER, P ;
LARSON, RE ;
MOOSEKER, MS .
CELL, 1993, 75 (01) :13-23
[3]   ISOLATION AND CHARACTERIZATION OF CALMODULIN GENES FROM XENOPUS-LAEVIS [J].
CHIEN, YH ;
DAWID, IB .
MOLECULAR AND CELLULAR BIOLOGY, 1984, 4 (03) :507-513
[4]   Missense mutations in the globular tail of myosin-Va in dilute mice partially impair binding of Slac2-a/melanophilin [J].
Fukuda, M ;
Kuroda, TS .
JOURNAL OF CELL SCIENCE, 2004, 117 (04) :583-591
[5]   Slac2-c (synaptotagmin-like protein homologue lacking C2 domains-c), a novel linker protein that interacts with Rab27, myosin Va/VIIa, and actin [J].
Fukuda, M ;
Kuroda, TS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (45) :43096-43103
[6]   Slac2-a/melanophilin, the missing link between Rab27 and myosin Va - Implications of a tripartite protein complex for melanosome transport [J].
Fukuda, M ;
Kuroda, TS ;
Mikoshiba, K .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (14) :12432-12436
[7]   Ca2+-dependent regulation of the motor activity of myosin V [J].
Homma, K ;
Saito, J ;
Ikebe, R ;
Ikebe, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (44) :34766-34771
[8]  
Huang JD, 1998, GENETICS, V148, P1963
[9]   Cell cycle regulation of myosin-V by calcium/calmodulin-dependent protein kinase II [J].
Karcher, RL ;
Roland, JT ;
Zappacosta, F ;
Huddleston, MJ ;
Annan, RS ;
Carr, SA ;
Gelfand, V .
SCIENCE, 2001, 293 (5533) :1317-1320
[10]   Myosin V: regulation by calcium, calmodulin, and the tail domain [J].
Krementsov, DN ;
Krementsova, EB ;
Trybus, KM .
JOURNAL OF CELL BIOLOGY, 2004, 164 (06) :877-886