Caron C et al. (1994) Worm Breeder's Gazette "Analysis of zyg-1, a Gene Required During the First Embryonic Divisions and For Formation of a Functional Vulva"

Caron C, Kemphues KJ

[Worm Breeder's Gazette, 1994]

ANALYSIS OF zyg-1, A GENE REQUIRED DURING THE FIRST EMBRYONIC DIVISIONS AND FOR FORMATION OF A FUNCTIONAL VULVA. Cathy Caron and Kenneth Kemphues, Cornell University, Ithaca, New York.

Zheng Zhou et al. (2001) International C. elegans Meeting "CED-12, A COMPONENT OF A RHO/RAC GTPASE SIGNALING PATHWAY, REGULATES CYTOSKELETAL REORGANIZATION AND CONTROLS CELL-CORPSE ENGULFMENT AND CELL MIGRATION IN C. elegans"

Alan Hall, Angell Shieh, Zheng Zhou, Erika Hartwieg, Emmanuelle Caron, Bob Horvitz

[International C. elegans Meeting, 2001]

During animal development, cells undergoing programmed cell death, or apoptosis, are rapidly engulfed and degraded by neighboring cells. The engulfment of apoptotic cells by their neighbors is an evolutionarily conserved process. In C. elegans , mutations in genes that define two partially redundant pathways block the engulfment of cell corpses, causing cell corpses to persist abnormally. In one of these pathways, ced-1 , ced-6 and ced-7 appear to act together to control cell-corpse recognition and to initiate phagocytosis. CED-1 is a transmembrane receptor similar to a mammalian scavenger receptor. CED-1 recognizes and clusters around cell-corpses to mediate their engulfment. ced-7 encodes an ABC transporter that promotes the recognition of cell corpses by CED-1, possibly by exposing phospholipids on the outer surface of the cell corpses. ced-6 encodes an adaptor-like protein that acts in engulfing cells. In the other engulfment pathway, ced-2 CrkII, ced-5 DOCK180, and ced-10 Rac are part of a Rac GTPase signaling pathway proposed to mediate cytoskeletal reorganization. We identified a new engulfment gene, ced-12 , in a large-scale genetic screen for engulfment-defective mutants. Like ced-2 , ced-5 , and ced-10 , ced-12 functions in both cell-corpse engulfment and distal tip cell migration. Genetic interaction studies showed that ced-12 acts in a pathway with ced-2 CrkII, ced-5 DOCK180, and ced-10 Rac GTPase in cell-corpse engulfment. We cloned ced-12 and found that it encodes a novel protein with a candidate SH3-binding motif. The CED-12 protein has both Drosophila and human counterparts. The Drosophila homolog Dced-12 could partially replace the function of ced-12 in C. elegans . CED-12 functions in engulfing cells to mediate cell-corpse engulfment. A CED-12::GFP fusion protein is localized to the cytoplasm in C. elegans . CED-12 interacts physically with CED-5, which contains an SH3 domain. When expressed in Swiss 3T3 fibroblast cells, CED-12 induced formation of filamentous actin structures in a manner dependent on the GTPase Rho. We propose that CED-12 is recruited to a CED-2/CED-5 protein complex through its interaction with CED-5 and regulates or effects Rho/Rac GTPase signaling, thereby leading to cytoskeletal reorganization by a mechanism that is evolutionarily conserved. We have performed a yeast two-hybrid screen for C. elegans proteins that interact with CED-12 and have identified a number of positive clones. Currently we are studying the functions of these potential CED-12 interacting proteins in the context of programmed cell death, cell-corpse engulfment, and cell migration.

MG de Bono et al. (1999) International C. elegans Meeting "The Genetics of C. elegans social behavior"

CI Bargmann, MG de Bono

[International C. elegans Meeting, 1999]

Natural isolates of C. elegans behave in one of two distinct ways on food. Solitary strains (e.g. N2) slow down in response to a bacterial lawn, disperse evenly across the lawn, and forage alone. Social strains accumulate where bacteria are thickest, aggregate together, and do not slow down on food until they join a clump. Behavioral differences between social and solitary strains are seen only in the presence of food. By a combination of genetic and molecular studies* we have shown that the behavioral differences between social and solitary wild strains are due to a single amino acid substitution in a single gene called npr-1 (pka bor-1 , and renamed by kind permission of Randy Cassada and the CGC). npr-1 encodes a G-protein coupled receptor that belongs to the neuropeptide Y family of seven transmembrane receptors. Predicted null mutations in npr-1 (neuropeptide receptor resemblence) make the solitary N2 strain take on social behavior. We are attempting to define the molecular and cellular circuitries that regulate social and solitary behaviors. We know that social behavior is not disrupted by mutations that abolish previously described sensory responses in C. elegans (e.g. che-3, che-13, odr-3, mec-3, ttx-3 ) but requires the cyclic nucleotide gated ion channel encoded by tax-2 and tax-4 , and the capsaicin receptor homolog osm-9 . tax-2 and tax-4 are expressed in ten overlapping sensory neurons. We are currently determining which of these neurons require tax-2/tax-4 activity for social behavior. To identify the circuit which represses social behavior in solitary animals, we are searching for the ligand for npr-1 . Based on homology, we predict that npr-1 will have a neuropeptide ligand. In collaboration with Marc Caron at Duke University we are attempting to set up an assay system in mammalian tissue culture cells that would allow us to test candidate ligands or C. elegans extracts for their ability to stimulate npr-1 . *de Bono and Bargmann, Cell, 94, 679-689