The cut locus of D. melanogaster is an integral part of a communication pathway between two different cell types of the ovary. Loss of cut function in the somatic follicle cells interferes with these communications, disrupting the structural integrity of the germline-derived cells enclosed within the follicular epithelium We have shown by genetic analyses that mutations in cyclic-AMP dependent Protein kinase A (Pka-C1), agnostic, a gene that affects cAMP metabolism, and cappuccino and ovarian tumor, two genes that influence cytoskeletal function, interact genetically with cut mutations in this process. These results led us to hypothesize that cut activity in the follicle cells regulates a signaling pathway that impinges on the function of agnostic, cappuccino, and ovarian tumor in the germline cells. In this proposal, the function of these genes in this novel pathway is analyzed using a four-pronged approach. First, we will determine the mechanism responsible for the response of cappuccino and ovarian tumor to cut- and cAMP-mediated signaling by examining the expression, localization and phosphorylation state of these proteins when these pathways are disrupted. Second, we will determine the mechanism used by cut and agnostic in regulating cAMP levels and Pka-C activity in the germline by measuring cAMP levels, Pka-C catalytic activity, and agnostic expression levels when cut function is disrupted. Third, we will determine the importance of localized Protein kinase A activity in regulating the morphology of the germline cells by asking whether ectopic expression of PKA constructions or a dominant negative AKAP fragment can produce a multinucleate cell phenotype. Finally, we ask whether an A-kinase anchoring protein uncovered by a deficiency that interacts with cut mediates germ cell cytoskeletal integrity. Together, these experiments will determine how a communication pathway transmits a signal from one cell type through Protein kinase A to the cytoskeleton of another cell type.
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| Jackson, Stephen M; Berg, Celeste A (2002) An A-kinase anchoring protein is required for protein kinase A regulatory subunit localization and morphology of actin structures during oogenesis in Drosophila. Development 129:4423-33 |
