Characterization of in vivo function of Shank using deletion mutants in Caenorhabditis elegans

초록

Shank gene encodes a protein that may function as molecular scaffolds in the postsynaptic density (PSD). Shank family members contain multiple domains for protein-protein interaction including ankyrin repeats, an SH3 domain, a PSD-95/Dlg/ ZO-1 (PDZ) domain, a proline-rich region and a sterile alpha motif domain. We have investigated that in vivo function of Shank with deletion mutations of shn-1 gene which is the only homologue and expressed in pharynx, intestine, vulva, and sperm in C. elegans. shn-1 deletion mutants (tm488 and ok1241) showed normal phenotypes in basic characters such as body size, morphology, life cycle and longevity, but had various minor defects in fertility, movement, rhythmic cycles and mating behaviors. shn-1(tm488) has reduced brood sizes, prolonged pumping rates in presence of food, and extended defecation cycles. These phenotypes were synergistically worsened in the double mutants of shn-1(tm488) and itr-1(sa73), inositol trisphosphate (IP3) receptor. Moreover, defects in egg-laying and movement were specifically observed in levamisole, an agonist for acetylcholine receptor, but not in serotonin treatments. Finally, shn-1 males have defects on male mating behaviors. Taken together, these results suggest that Shank has important roles in controlling rhythmic cycles and behaviors such as pumping, defecation, egg-laying, and mating in C. elegans. 55