The molecular controls governing the formation of organ structure in the development are less understood. The Caenorhabditis elegans excretory system, like the renal organs of other animals, is believed to regulate osmoregulation and water elimination1. The excretory cell extends tubular processes, called canals, along the basolateral surface of the epidermis. Mutations in the
exc-5 gene cause tubulocystic defects in the excretory canal. Here we report that
exc-5 encodes a protein homologous to guanine nucleotide exchange factors (GEFs). EXC-5 contains, in order, a Dbl/Plecstrin homology (DH/PH) domain, a cysteine-rich FYVE domain and a second PH element. This motif architecture is similar to that of FGD1 (ref. 2), which is responsible for faciogenital dysplasia or Aarskog-Scott syndrome. Ultrastructural results suggest that
exc-5 is required for the proper placement of cytoskeleton at the apical epithelial surface. Furthermore, EXC-5 associates with KEL-2, a protein similar to the actin-associated protein Drosophila Kelch3,4. We speculate that EXC-5 controls structural organization of the excretory canal by linking between the actin cytoskeleton and a Rho family GTPase. References: 1. Nelson, F. K., Albert, T. S. & Riddle, D. L. Fine structure of the Caenorhabditis elegans secretory-excretory system. J. Ultrastruct. Res. 82, 156-171 (1983) 2. Broeks, A., Janssen, H. W., Calafat, J. & Plasterk, R. K. A P-glycoprotein protects Caenor ha bditis elegans against natural toxins. EMBO J. 14, 1858-1866 (1995) 3. Pasteris, N. G. et al. Isolation and characterization of the faciogenital dysplasia (Aarskog-scott syndrome) gene: a putative Rho/Rac guanine nucleotide exchange factor. Cell 79, 669-678 (1994) 4. Chitwood, M. B. & Chitwood, B. G. The excretory system. In Introduction to Nematology:(eds. Chitwood, B. G. & Chitwood, M. B.; University Park Press, Baltimore) 126-135 (1974)