Ostap Laboratory
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Selected Recent Publications

For a complete list of Ostap Laboratory publications from PubMed, click here.

Control of myosin-I force sensing by alternative splicing.
Joseph M. Laakso, John H. Lewis, Henry Shuman, and E. Michael Ostap
PNAS, 107:698-702.

isoformsMyosin-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.

View paper on PNAS website, or send email to request PDF file.

 

Publication imageryMyosin-I can act as a molecular force sensor.
Joseph M. Laakso, John H. Lewis, Henry Shuman, and E. Michael Ostap
Science, 321:133-136.

The ability to sense molecular tension is crucial for a wide array of cellular processes, including the detection of auditory stimuli, control of cell shape, and internalization and transport of membranes. We show that myosin I, a motor protein that has been implicated in powering key steps in these processes, dramatically alters its motile properties in response to tension. We measured the displacement generated by single myosin I molecules, and we determined the actin-attachment kinetics with varying tensions using an optical trap. The rate of myosin I detachment from actin decreases >75-fold under tension of 2 piconewtons or less, resulting in myosin I transitioning from a low (<0.2) to a high (>0.9) duty-ratio motor. This impressive tension sensitivity supports a role for myosin I as a molecular force sensor.

 

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