In multicellular organisms, cell-cell junctions are involved in all aspects of tissue morphogenesis, including regulation of cell shape and movement. To establish junctions, cytoplasmic proteins that interact with the actin cytoskeleton must stabilize adhesion molecules. For example, catenins connect cadherins to the cytoskeleton and mutations in catenin proteins significantly impact morphogenesis. A previously isolated hypomorphic allele of the C. elegans ?-catenin homolog,
hmp-1(
fe4) , exhibits ~70% lethality and body shape defects (Pettitt, et al., 2003, JCB 162, 15-22). In continuing efforts to identify regulators of the cadherin-catenin complex, we conducted a genome-wide RNAi screen to identify genes whose loss of function enhances the
hmp-1(
fe4) phenotype. We uncovered MAGI-1, a vert ebrate tight junction protein known to interact with actin-binding proteins (Patrie, et al., 2002, JBC 277, 30183-90). We have shown C. elegans MAGI-1 genetically interacts with
hmp-1 /?-catenin and
hmp-2 /?-catenin, suggesting MAGI-1 may modulate cadherin-catenin function during morphogenesis. MAGI-1 localizes at the C. elegans apical junction, but is surprisingly basal to the cadherin-catenin complex. In addition, MAGI-1 junction localization is not dependent on ?-catenin, in contrast to what has been shown in tissue culture (Dobrosotskaya, et al., 2000, BBRC 270, 903-09). We are currently examining if MAGI-1 modulates actin dynamics during morphogenesis and we are characterizing proteins that potentially interact with MAGI-1 to further assess how MAGI-1 functions in a living organism.