inositol-1-4-5-trisphosphate and Disorders-of-Sex-Development

Activity of LET-23, the C. elegans homolog of the epidermal growth factor receptor, is required in multiple tissues. RAS activation is necessary and sufficient for certain LET-23 functions. We show that an inositol trisphosphate receptor can act as a RAS-independent, tissue-specific positive effector of LET-23. Moreover, an inositol trisphosphate kinase negatively regulates this transduction pathway. Signals transduced by LET-23 control ovulation through changes in spermathecal dilation, possibly dependent upon calcium release regulated by both IP3 and IP4. Our results demonstrate that one mechanism by which receptor tyrosine kinases can evoke tissue-specific responses is through activation of distinct signal transduction cascades in different tissues.

Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Calcium; Calcium Channels; Disorders of Sex Development; Enzyme Activation; Epidermal Growth Factor; ErbB Receptors; Female; Helminth Proteins; Inositol 1,4,5-Trisphosphate; Inositol 1,4,5-Trisphosphate Receptors; Male; Molecular Sequence Data; Mutagenesis; Ovulation; Protein-Tyrosine Kinases; ras Proteins; Receptors, Cytoplasmic and Nuclear; Sequence Homology, Amino Acid; Signal Transduction; Spermatogenesis