The Insulin Receptor is an Autonomous Nutrient Sensor Regulating Germline Cyst Survival. R.A. Kohanski. Biochem & Molec Biol, Box 1020, Mount Sinai Sch Medicine, New York, NY.

   Under amino acid starvation conditions, two checkpoints are evident in egg chamber development: vitellinization halts and germline cysts die in germarial region 2, just prior to becoming enveloped by somatic follicle cells. Both checkpoints are observed in four combinations of heterozygous hypomorphic alleles of the Drosophila insulin receptor homologue (dinr) that were viable, well-fed, but female-sterile. The lack of vitellinization has also been reported in chico1/1 females, but we did not observe significantly increased cyst death in the ovaries of these flies. Since egg chamber development is subject to control by neurohemal and fat body-secreted factors, and these can be abnormal in dinr and chico mutants, we tested the autonomy of cyst death by generating germline and follicle cell clones of hypomorphic and null dinr mutants. Germline clones of the hypomorphic alleles showed death in the cyst as late as stage 3 and at least one dinr mutant produced mature egg chambers. Follicle cell clones were viable, including clones of the dinr null mutant. However, germline clones of the dinr null mutant died at the germarial 2a/2b border, producing a phenocopy of the amino acid starvation-inducible cyst death in fed flies that have the fat body and neurohemal factors needed to support egg chamber development. Finally, Daktq1 which causes cell death in homozygous embryos did not cause premature cyst death in germline clones, ruling out its involvement in this anti-apoptotic function of DINR. In addition to the known DINR pathways regulating cell division and cell growth, these results demonstrate a cell type-specific nutrient-sensing anti-apoptotic pathway that is autonomous of other starvation effects. This indicates that the insulin receptor is a member of the family of nutrient-sensing regulatory proteins that includes dTOR, SIR2, and GCN2.