Myth-Ferm Myosins have Roles in Regulating Actin Polymerization

Abstract

The MyTH-FERM (MF) myosins are a subgroup of actin-based motors characterized by the presence of one or two adjacent MyTH (myosin tail homology 4)/FERM (band 4.1, ezrin, radixin, moesin) domains in their C-terminal tail regions. Although the MF myosins Myo7, Myo10, Myo15 and Myo44 are phylogenetically distinct, they have several characteristics in common. Each of these MF myosins has a striking localization to the tips of structures formed by parallel actin bundles such as filopodia and stereocilia and the different myosins play a role in the extension of either filopodia (Myo10) or stereocilia (Myo7A, Myo15) in Metazoa and filopod extension in Amoebozoa (Myo7). Their shared roles in the extension of parallel actin bundles is consistent with each of these myosins transporting or anchoring regulators of actin polymerization to the growing tip. Surprisingly, the amoeboid Myo44 is not needed for the formation of filopodia. However, Myo44 is rapidly recruited to the plasma membrane following chemotactic stimulation, consistent with its role in mediating the transmission of chemotactic signals that generate cell polarity to the actin cytoskeleton. Myo44 is necessary for the rapid activation of actin polymerization (∼5 sec) following chemotactic stimulation and is required for activating Ras, a critical small GTPase that promotes the rapid, localized polymerization of actin at side of the cell closest to the stimulus. These results establish a new role for MF myosins in signaling to the actin cytoskeleton and establish a general role for this group of myosins in regulating actin polymerization.This work was supported by grants from the NSF and AHA.