Myosin IC generates power over a range of loads via a new tension-sensing mechanism.
Myosin IC (myo1c), a widely expressed motor protein that links the actin cytoskeleton to cell membranes, has been associated with numerous cellular processes, including insulin-stimulated transport of GLUT4, mechanosensation in sensory hair cells, endocytosis, transcription of DNA in the nucleus, exocytosis, and membrane trafficking. The molecular role of myo1c in these processes has not been defined, so to better understand myo1c function, we utilized ensemble kinetic and single-molecule techniques to probe myo1c's biochemical and mechanical properties. Utilizing a myo1c construct containing the motor and regulatory domains, we found the force dependence of the actin-attachment lifetime to have two distinct regimes: a force-independent regime at forces < 1 pN, and a highly force-dependent regime at higher loads. In this force-dependent regime, forces that resist the working stroke increase the actin-attachment lifetime. Unexpectedly, the primary force-sensitive transition is the isomerization that follows ATP binding, not ADP release as in other slow myosins. This force-sensing behavior is unique amongst characterized myosins and clearly demonstrates mechanochemical diversity within the myosin family. Based on these results, we propose that myo1c functions as a slow transporter rather than a tension-sensitive anchor.
The Pennsylvania Muscle Institute and Department of Physiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104-6085, USA.
Michael J
MJ
Greenberg
Tianming
T
Lin
Yale E
YE
Goldman
Henry
H
Shuman
E Michael
EM
Ostap
D000199:Actins / Q000502:physiology*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena; D002147:Calmodulin / Q000378:metabolism; D002352:Carrier Proteins / Q000502:physiology*; D002853:Chromatography, Liquid; D016013:Likelihood Functions; D051379:Mice; D009129:Muscle Tonus / Q000502:physiology*; D024461:Myosin Type I / Q000502:physiology*; D052898:Optical Tweezers
D000199:Actins; D002147:Calmodulin; D002352:Carrier Proteins; C470422:Myo1c protein, mouse; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D024461:Myosin Type I