| Description |
The morphological integrity and coordinated functions of tissues depends on specialized cell junctions that serve as sites of cytoskeletal anchorage, cell-cell adhesion and communication. The ALP/Enigma family of PDZ-LIM proteins plays a role in cytoskeletal anchorage and mutations in at least one member of this family are associated with human cardiomyopathy. Here I describe the analysis of the C. elegans eat-1 gene that encodes the entire nematode ALP/Enigma protein family. Mutations in eat-1 result in pharyngeal pumping, egg-laying, and locomotory defects, phenotypes consistent with compromised muscle function. EAT-1 proteins are expressed in muscle cells, where they localize to actin anchorage and muscle attachment sites, and in epithelial cells where they localize to apical cell junctions. Consistent with this subcellular distribution, on an ultrastructural level, eat-1 mutants display defects in body wall muscle cell-cell adhesion. In the pharynx, EAT-1 is required for the accumulation of the apical junction component, AJM-1, that has an established role in junctional architecture and integrity. These data indicate that EAT-1 proteins are required for both body wall muscle cell-cell adhesion and pharyngeal apical junction integrity. The cellular defect responsible for these functional deficiencies occurs at the level of cell-cell junctions. I detect disturbances in both the molecular organization and adhesive capacity of these specialized regions of the cell surface in animals with mutations that compromise ALP/Enigma function. Thus these studies have revealed a critical and novel role for ALP/Enigma proteins for the integrity of cell junctions. |
