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MBC in Press, published online ahead of print May 7, 2004
Mol. Biol. Cell 10.1091/mbc.E04-01-0039

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Submitted on January 16, 2004
Revised on March 26, 2004
Accepted on April 26, 2004

IRI-1, a LIN-15B homologue, interacts with IP3 receptors and regulates gonadogenesis, defecation and pharyngeal pumping in C. elegans

Denise S. Walker1, Sung Ly1, Nicholas J.D. Gower1, and Howard A. Baylis1*

1 Department of Zoology, University of Cambridge, Downing Street, Cambridge, CB2 3EJ, U.K.

* Corresponding author. E-mail address: hab{at}mole.bio.cam.ac.uk.

Inositol 1,4,5 triphosphate receptors (IP3Rs) are ligand-gated Ca2+ channels that control Ca2+ release from intracellular stores. They are central to a wide range of cellular responses. IP3Rs in C. elegans are encoded by a single gene, itr-1, and are widely expressed. Signaling through IP3 and IP3Rs is important in ovulation, control of the defecation cycle, modulation of pharyngeal pumping rate and embryogenesis. To further elucidate the molecular basis of the diversity of IP3R function, we used a yeast two-hybrid screen to search for proteins that interact with ITR-1. We identified an interaction between ITR-1 and IRI-1, a previously uncharacterised protein with homology to LIN-15B. Iri-1 is widely expressed, and its expression overlaps significantly with that of itr-1. In agreement with this observation, iri-1 functions in known itr-1 mediated processes, namely, up-regulation of pharyngeal pumping in response to food, and control of the defecation cycle. Knockdown of iri-1 in an itr-1 loss-of-function mutant potentiates some of these effects, and sheds light on the signaling pathways that control pharyngeal pumping rate. Knockdown of iri-1 expression also results in a sterile, evl phenotype, as a consequence of failures in early Z1/Z4 lineage divisions, such that gonadogenesis is severely disrupted.




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