Calmodulin controls adaptation of mechanoelectrical transduction by hair cells of the bullfrog's sacculus.
Deflection of the mechanically sensitive hair bundle atop a hair cell opens transduction channels, some of which subsequently reclose during a Ca2+-dependent adaptation process. Myosin I in the hair bundle is thought to mediate this adaptation; in the bullfrog's hair cell, the relevant isozyme may be the 119-kDa amphibian myosin I beta. Because this molecule resembles other forms of myosin I, we hypothesized that calmodulin, a cytoplasmic receptor for Ca2+, regulates the ATPase activity of myosin. We identified an approximately 120-kDa calmodulin-binding protein that shares with hair-bundle myosin I the properties of being photolabeled by vanadate-trapped uridine nucleotides and immunoreactive with a monoclonal antibody raised against mammalian myosin I beta. To investigate the possibility that calmodulin mediates Ca2+-dependent adaptation, we inhibited calmodulin action and measured the results with two distinct assays. Calmodulin antagonists increased photolabeling of hair-bundle myosin I by nucleotides. In addition, when introduced into hair cells through recording electrodes, calmodulin antagonists abolished adaptation to sustained mechanical stimuli. Our evidence indicates that calmodulin binds to and controls the activity of hair-bundle myosin I, the putative adaptation motor.
Walker
R G
RG
Howard Hughes Medical Institute and Laboratory of Sensory Neuroscience, The Rockefeller University, New York, NY 10021-6399, USA.
Hudspeth
A J
AJ
D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D000818:Animals; D001307:Auditory Perception / Q000502:physiology*; D002147:Calmodulin / Q000502:physiology*; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D006198:Hair Cells, Auditory / Q000502:physiology*; D008969:Molecular Sequence Data; D009218:Myosins / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D011892:Rana catesbeiana; D015398:Signal Transduction; D013314:Stress, Mechanical
D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; D010455:Peptides; D009218:Myosins