Myo1c Binds Tightly and Specifically to Phosphatidylinositol 4,5-Bisphosphate and Inositol 1,4,5-Trisphosphate

Myosin-I is the single-headed member of the myosin superfamily that associates with acidic phospholipids through its basic tail domain. Membrane association is essential for proper myosin-l localization and function. However, little is known about the physiological relevance of the direct association of myosin-I with phospholipids or about phospholipid headgroup-binding specificity. To better understand the mechanism of myosin-l-membrane association, we measured effective dissociation constants for the binding of a recombinant myolc tail construct (which includes three IQ domains and bound calmodulins) to large unilamellar vesicles (LUVs) composed of phosphatidylcholine and various concentrations of phosphatidylserine (PS) or phosphatidylinositol 4,5bisphosphate (PIP₂). We found that the myolc-tail binds tightly to LUVs containing >60% PS but very weakly to LUVs containing physiological PS concentrations (