INVESTIGATING THE FUNCTIONAL ROLES OF CRF-BINDING PROTEIN HOMOLOGUE IN THE RESPONSE TO PHYSIOLOGICAL STRESSES IN DROSOPHILA

Stress causes a characteristic set of physiological and behavioral responses in all animals. The mammalian hormone, corticotropin-releasing factor (CRF), coordinates these stress responses to a variety of different stresses. CRF has three binding partners, including two receptors and a binding protein, and it is the receptors that initiate signaling pathways ultimately responsible for alterations in behavioral and physiological program. In contrast, the binding protein functions as a negative regulator of CRF signaling and is a critical element in coordinating dynamic aspects of stress responses. In Drosophila, the DH44 hormone is homologous to CRF and binds to two CRF-related receptors, DH44-R1 and DH44-R2. We suspect, based on this homology, that DH44 is critical in modulating the Drosophila stress response. We have identified a CRF-BP homolog in Drosophila, encoded by the gene CG15537. CG15537 possesses 60% sequence similarity to mammalian CRF-BP. Various stressors alter CRF-BP expression and, we observe changes in CG15537 expression coincident with the presentation of different stressors. Similar to CRF-BP expression in mammals, CG15537 is widely expressed throughout the Drosophila CNS. Furthermore, DH44 and its putative binding protein are co-localized in the Drosophila adult brain, which parallels the observations that CRF-BP is co-localized with CRF in the mammalian CNS. We find that CG15537 functions as a DH44-BP, through direct assessment of binding. Increased expression levels of DH44-BP causes increased survival under three different stresses. Surprisingly, decreased expression of DH44-BP also leads to enhanced survival under stress. Animals with either increased or decreased expression levels have similar behavioral phenotypes, including reduced starvation-induced hyperactivity and repressed reproductive output. Furthermore, we propose a model which reconciles the identical phenotype, and predicts that DH44-BP expression levels both is required for the onset and termination of the stress responses.

Grantor dc:publisher

Wake Forest University

Year dc:date.issued

2010

Author dc:creator

• Hector, Clare

• Drosophila

Language dc:language.iso

en_US

Handle dc:identifier.uri

http://hdl.handle.net/10339/14798

OAI identifier oai:identifier

oai:wakespace.lib.wfu.edu:10339/14798