It is well known that a significant fraction of cellular mRNAs and the protein synthetic machinery in vivo are transported on, and anchored to, actin filaments. Localized anchorage of mRNA (targeting) and protein synthesis is believed to define cell polarity and pattern formation during morphogenesis. The failure to target mRNA is strongly correlated with loss of cell polarity and metastatic potential in adenocarcinoma cells. More direct experiments indicate that localization to the leading edge of mRNAs that code for beta-actin, and Arp3 define the leading edge and subsequent direction of cell crawling in the absence of extracellular signals. The major G-protein that regulates polypeptide elongation during protein synthesis, EF1a, is an actin binding protein that appears to play a central role in defining the interaction between actin filaments and the translational apparatus. In this proposal we will test two key hypotheses for the role of mRNA targeting in cell motility and, in particular, the role of EF1a in facilitating targeting: 1. mRNAs for beta-actin and Arp3, when localized to the leading edge, determine cell polarity. 2. The EF1a-F-actin complex is the scaffold to which mRNAs, with a beta-actin mRNA-like zipcode, become anchored.
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