Selected Recent Publications

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

Myosin-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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Myo1c binds phosphoinositides through a putative PH domain.
David E. Hokanson, Joseph M. Laakso, Tianming Lin, David Sept, and E. Michael Ostap
Mol. Biol. Cell., 17:4856-4865.

Myo1c is a member of the myosin superfamily that binds PIP2, links the actin cytoskeleton to cellular membranes, and plays roles in mechano-signal transduction and membrane trafficking. We located and characterized two distinct membrane binding sites within the regulatory and tail domains of this myosin. By sequence, secondary structure, and ab initio computational analysis, we identified a phosphoinositide binding site in the tail to be a putative pleckstrin homology (PH) domain. Point mutations of residues known to be essential for poly-phosphoinositide binding in previously characterized PH domains inhibit myo1c binding to PIP2 in vitro, disrupt in vivo membrane binding, and disrupt cellular localization. The extended sequence of this binding site is conserved within other myosin-I isoforms, suggesting they too contain this putative PH domain. We also characterized a previously identified membrane binding site within the IQ motifs in the regulatory domain. This region is not phosphoinositide specific, but binds anionic phospholipids in a calcium dependent manner. However, this site is not essential for in vivo membrane binding.

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