Key result
Alternative splicing of the myo1b light chain binding domain regulates its force sensing, with the magnitude of tension sensitivity linearly related to the number of IQ motifs.
Alternative splicing in the light chain binding domain of myo1b is a key regulator of force sensing and tension sensitivity.
May inform cellular force models; leaves open translation to human cardiovascular mechanics.
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.
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Laakso et al. (2009) studied this question. Alternative splicing of myo1b light chain binding domain vs. Different splice isoforms (myo1ba, myo1bb, myo1bc, myo1bIQ) was evaluated on Force-dependent actin-detachment kinetics (ddet). Alternative splicing of the myo1b light chain binding domain regulates its force sensing, with the magnitude of tension sensitivity linearly related to the number of IQ motifs.
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