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Vol. 14, Issue 6, 2492-2507, June 2003

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Caenorhabditis elegans UNC-98, a C2H2 Zn Finger Protein, Is a Novel Partner of UNC-97/PINCH in Muscle Adhesion Complexes

Kristina B. Mercer ^*, Denise B. Flaherty ^*, Rachel K. Miller ^* , Hiroshi Qadota , Tina L. Tinley ^*  , Donald G. Moerman , and Guy M. Benian ^* ||

^* Department of Pathology, Emory University, Atlanta, Georgia 30322; Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, Georgia 30322; and Department of Zoology, University of British Columbia, Vancouver, British Columbia V6T1Z4, Canada

Submitted October 22, 2002; Revised January 29, 2003; Accepted February 26, 2003
Monitoring Editor: Mary C. Beckerle

To further understand the assembly and maintenance of the muscle contractile apparatus, we have identified a new protein, UNC-98, in the muscle of Caenorhabditis 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 nonmuscle cells. UNC-98 is a novel 310-residue polypeptide consisting of four C2H2 Zn fingers and several possible nuclear localization signal and nuclear export signal sequences. By use of UNC-98 antibodies and green fluorescent protein 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 (fourth) 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.

Present address: Southwest Foundation for Biomedical Research, San Antonio, TX 78245.

^|| Corresponding author. E-mail address: pathgb{at}emory.edu.

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