Calcium regulation of myosin-I tension sensing.
Myo1b is a myosin that is exquisitely sensitive to tension. Its actin-attachment lifetime increases > 50-fold when its working stroke is opposed by 1 pN of force. The long attachment lifetime of myo1b under load raises the question: how are actin attachments that last >50 s in the presence of force regulated? Like most myosins, forces are transmitted to the myo1b motor through a light-chain binding domain that is structurally stabilized by calmodulin, a calcium-binding protein. Thus, we examined the effect of calcium on myo1b motility using ensemble and single-molecule techniques. Calcium accelerates key biochemical transitions on the ATPase pathway, decreases the working-stroke displacement, and greatly reduces the ability of myo1b to sense tension. Thus, calcium provides an effective mechanism for inhibiting motility and terminating long-duration attachments.
Pennsylvania Muscle Institute and Department of Physiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
John H
JH
Lewis
Michael J
MJ
Greenberg
Joseph M
JM
Laakso
Henry
H
Shuman
E Michael
EM
Ostap
D000199:Actins / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology*; D055595:Mechanical Phenomena; D009068:Movement / Q000187:drug effects; D024461:Myosin Type I / Q000378:metabolism*; D011817:Rabbits
D000199:Actins; D024461:Myosin Type I; D002118:Calcium