Calcium sensitivity of the cross-bridge cycle of Myo1c, the adaptation motor in the inner ear.
The class I myosin Myo1c is a mediator of adaptation of mechanoelectrical transduction in the stereocilia of the inner ear. Adaptation, which is strongly affected by Ca(2+), permits hair cells under prolonged stimuli to remain sensitive to new stimuli. Using a Myo1c fragment (motor domain and one IQ domain with associated calmodulin), with biochemical and kinetic properties similar to those of the native molecule, we have performed a thorough analysis of the biochemical cross-bridge cycle. We show that, although the steady-state ATPase activity shows little calcium sensitivity, individual molecular events of the cross-bridge cycle are calcium-sensitive. Of significance is a 7-fold inhibition of the ATP hydrolysis step and a 10-fold acceleration of ADP release in calcium. These changes result in an acceleration of detachment of the cross-bridge and a lengthening of the lifetime of the detached M-ATP state. These data support a model in which slipping adaptation, which reduces tip-link tension and allows the transduction channels to close after an excitatory stimulus, is mediated by Myo1c and modulated by the calcium transient.
Adamek
Nancy
N
Department of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, United Kingdom.
Coluccio
Lynne M
LM
Geeves
Michael A
MA
D000244:Adenosine Diphosphate / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology*; D007758:Ear, Inner / Q000737:chemistry*; D006868:Hydrolysis; D007700:Kinetics; D040542:Mechanotransduction, Cellular; D008954:Models, Biological; D020409:Molecular Motor Proteins; D024461:Myosin Type I / Q000378:metabolism*
D020409:Molecular Motor Proteins; D000244:Adenosine Diphosphate; D000251:Adenosine Triphosphatases; D024461:Myosin Type I; D002118:Calcium