CD38 and CD157 have been identified as mammalian forms of ADP-ribosyl cyclase (ADPRC). Recently novel membrane bound and cytosolic ADPRCs that are distinct from CD38 and CD157 have been identified in various tissues by our laboratory as well as others. Recently, evidence has indicated the presence of ADPRC in tissues lacking CD38. From this it is clear that there are multiple forms of mammalian ADPRC, many of which have not yet been identified or characterized. The overall goal of the research presented in this thesis was to identify and characterize the novel cytosolic cyclase(s) present in the heart cytosol and determine the mechanism(s) by which cytosolic cyclase(s) are regulated. Previously it has been shown that Aplysia ADPRC, CD38 and CD157 share approximately 30% sequence identity. There are two main features shared by each of these members of the ADPRC family including a conserved region near the center and ten conserved cysteine residues that can be perfectly aligned. We used a molecular approach to identify potential candidates for the cytosolic protein (or other yet unidentified ADPRCs) based on a conserved protein motif search of the mouse genome to identify proteins that shared the feature of the conserved cysteine residues. The existence of novel cyclases has implications for a broad range of cellular processes that are influenced by calcium signaling. Characterization and identification of novel ADPRCs may provide key insight into the function of the novel cyclase(s) as well as interaction and relationships to other members of the ADPRC family, which will further elucidate the complexities of calcium signaling.
University of Minnesota Ph.D. dissertation. August 2011. Major: Pharmacology. Advisor: Timothy F. Walseth Ph.D. 1 computer file (PDF); iv, 154 pages.
Hirte, Renee Marie.
Identification and characterization of novel ADP-ribosyl cyclase family members.
Retrieved from the University of Minnesota Digital Conservancy,
Content distributed via the University of Minnesota's Digital Conservancy may be subject to additional license and use restrictions applied by the depositor.