C. elegans UNC-98, a C2H2 Zn finger protein, is a novel partner of UNC-97 / PINCH in muscle adhesion complexes

In order to further understand the assembly and maintenance of the muscle contractile apparatus, we have identified a new protein, UNC-98, in the muscle of C. elegans. unc-98 mutants display reduced motility and a characteristic defect in muscle structure. We show that the major defect in the mutant muscle is in the M-lines and dense bodies (Z-line analogs). Both functionally and compositionally, nematode M-lines and dense bodies are analogous to focal adhesions of non-muscle cells. UNC-98 is a novel 310 residue polypeptide consisting of four C2H2 Zn fingers and several possible NLS and NES sequences. By use of UNC-98 antibodies and GFP fusions (to full length UNC-98 and UNC-98 fragments), we have shown that UNC-98 resides at M-lines, muscle cell nuclei, and possibly at dense bodies. Furthermore, we demonstrated that (1) the N-terminal 106 amino acids are both necessary and sufficient for nuclear localization, and (2) the C-terminal (4 th) Zn finger is required for localization to M-lines and dense bodies. UNC-98 interacts with UNC-97, a C. elegans homolog of PINCH. We propose that UNC-98 is both a structural component of muscle focal adhesions, and a nuclear protein that influences gene expression.