Control of myosin-I force sensing by alternative splicing.
Myosin-Is are molecular motors that link cellular membranes to the actin cytoskeleton, where they play roles in mechano-signal transduction and membrane trafficking. Some myosin-Is are proposed to act as force sensors, dynamically modulating their motile properties in response to changes in tension. In this study, we examined force sensing by the widely expressed myosin-I isoform, myo1b, which is alternatively spliced in its light chain binding domain (LCBD), yielding proteins with lever arms of different lengths. We found the actin-detachment kinetics of the splice isoforms to be extraordinarily tension-sensitive, with the magnitude of tension sensitivity to be related to LCBD splicing. Thus, in addition to regulating step-size, motility rates, and myosin activation, the LCBD is a key regulator of force sensing. We also found that myo1b is substantially more tension-sensitive than other myosins with similar length lever arms, indicating that different myosins have different tension-sensitive transitions.
Laakso
Joseph M
JM
Department of Physiology, Pennsylvania Muscle Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Lewis
John H
JH
Shuman
Henry
H
Ostap
E Michael
EM
D000199:Actins / Q000737:chemistry / Q000378:metabolism; D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D007700:Kinetics; D016013:Likelihood Functions; D024461:Myosin Type I / Q000737:chemistry* / Q000235:genetics*; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D051381:Rats; D015398:Signal Transduction
D000199:Actins; C104297:Myo1b protein, rat; D020033:Protein Isoforms; D024461:Myosin Type I