Item Details

abstract

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.

subject

Drosophila

CRF

Stress

contributor

Hector, Clare (author)

Muday, Gloria (committee chair)

Johnson, Erik (committee member)

Lord, Pat (committee member)

date

2010-05-07T18:55:15Z (accessioned)

2010-06-18T18:58:49Z (accessioned)

2010-05-07T18:55:15Z (available)

2010-06-18T18:58:49Z (available)

2010-05-07T18:55:15Z (issued)

degree

Biology (discipline)

identifier

http://hdl.handle.net/10339/14798 (uri)

language

en_US (iso)

publisher

Wake Forest University

rights

Release the entire work for access only to the Wake Forest University system for one year from the date below. After one year, release the entire work for access worldwide. (accessRights)

title

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

type

Thesis