Education & Training
- Louisiana State University, 1993
Areas of Interests
- Research Interest
- Mechanisms of adenylyl cyclase regulation
Mechanisms of adenylyl cyclase regulation
The enzyme adenylyl cyclase synthesizes the intracellular second messenger cyclic AMP, which plays a key role in functions ranging from control of heart rate and force of contraction to learning and memory. Many hormones and drugs mediate their actions by binding to G protein-coupled receptors that regulate cAMP production. Our laboratory is using structural, biochemical, live-cell imaging, and molecular biology techniques to understand the complex regulation of adenylyl cyclase by heterotrimeric GTP-binding proteins and regulators of G protein signaling (RGS proteins).
Another major question in the laboratory is how the fidelity of signaling is maintained within a cell. Cyclic AMP is a small diffusible molecule, yet many hormones stimulate cAMP production but elicit different biological responses. We are examining how localization of adenylyl cyclase to specific complexes within the membrane plays a role in cellular signaling. We have discovered that specific anchoring proteins of cAMP-dependent kinase (AKAPs) recruit adenylyl cyclase as well as other regulatory molecules. These signaling complexes have important roles at post-synaptic densities in the brain to control glutamate signaling and also function in the heart to control contractile events. We are currently using biochemical and functional studies in brain and heart to further define the nature of adenylyl cyclase complexes and to understand how specificity of signaling is generated and maintained.
LAB WEBSITE: www.Dessauer-Lab.com
- Dvir, M., Strulovich, R., Sachyani, D., Cohen, I.B., Haitin, Y., Dessauer, C.W., Pongs, O., Kass, R.S., Hirsch, J., and Attali, B. (2014). Long QT mutations disrupt IKS regulation by PKA and PIP2 at the same KCNQ1 helix C-KCNE1 interface. J. Cell Sci., 127:3943-55.
- Kahanovitch U., Tsemakhovich V., Berlin, S., Rubinstein, M., Styr, B., Castel, R., Peleg, S., Tabak, G., Dessauer, C.W., Ivanina, T. and Dascal, N. (2014). Recruitment of Gβγ controls the basal activity of GIRK channels: crucial role of distal C-terminus of GIRK1. J of Physiol, 592: 5373-90.
- Tselnicker, I.F., Tsemakhovich, V., Rishal, I., Dessauer, C.W., and Dascal, N. (2014). Dual regulation of G proteins and the G protein-activated K+ channels by lithium. Proc. Natl. Acad. Sci., 111: 5018-23.
- Brand, C..S., Hocker, H.J., Gorfe, A.A., Cavasotto, C.N., Dessauer, C.W. (2013). Isoform selectivity of adenylyl cyclase inhibitors: characterization of known and novel compounds. J Pharmacol Exp Ther. 347(2): 265-75.
- Conley, J.M., Brand, C.S., Bogard, A.S., Pratt, E.P.S., Xu, R., Hockerman, G.H., Ostrom, R., Dessauer, C.W., and Watts, V.J. (2013). Development of a high-throughput screening paradigm for the discovery of small molecule modulators of adenylyl cyclase: Identification of an adenylyl cyclase 2 inhibitor. JPET 347(2): 276-87.
- Efendiev, R., Bavencoffe, A., Hu, H., Zhu, M.X., Dessauer, C.W. (2013). Scaffolding by A-Kinase Anchoring Protein enhances functional coupling between adenylyl cyclase and TRPV1 channel. J Biol Chem. 288, 3929-3937.
- Scott, JD, Dessauer, CW, Tasken, K. (2013). Creating order from chaos: Cellular regulation by kinase anchoring. Annual Review of Pharmacology and Toxicology 53:187-210.
- Dessauer CW and Sadana R. (2012) Adenylyl Cyclase. Encyclopedia of Signaling Molecules, Springer publishing, pp 59-66.
- Efendiev R, Bavencoffe A, Hu H, Zhu MX, Dessauer CW. (2012) Scaffolding by A-Kinase Anchoring Protein Enhances Functional Coupling between Adenylyl Cyclase and TRPV1 Channel. J Biol Chem Dec 21. [Epub ahead of print] .
- Ejendal KFK, Dessauer CW, Hebert TE, and Watts VJ. (2012) Dopamine D2 receptor-mediated heterologous sensitization of AC5 requires signalosome assembly. J Signal Trans, 2012: 210324-30.
- Li Y, Chen L, Kass RS, and Dessauer CW. (2012) The A-kinase anchoring protein Yotiao facilitates complex formation between type 9 adneylyl cyclase and the IKs potassium channel in heart. J. Biol. Chem. 287(35):29315-29824.
- Scott JD, Dessauer CW, and Tasken K. (2012) Creating order from chaos: Cellular regulation by kinase anchoring. Ann Rev Pharm & Tox, 53:187-210. (Epub 2012 Oct 8).
- Xie K, Masuho I, Brand C, Dessauer CW, and Martemyanov K. (2012) Striatal G protein regulator RGS9-2/Gβ5 controls sensitization and temporal signaling of type 5 adenylyl cyclase. Science Signaling, 5(239):ra63.
- Pulliainen AT, Pieles K, Brand CS, Hauert B, Böhm A, Quebatte M, Wepf A, Gstaiger M, Aebersold R, Dessauer CW, and Dehio C. (2012) Bacterial effector binds host cell adenylyl cyclase to potentiate Gαs-dependent cAMP production. Proc. Natl. Acad. Sci. 109:9581-9586.
- Berlin S, Tsemakhovich VA, Castel R, Ivanina T, Dessauer CW, Keren-Raifman T, Dascal N. (2011) Two Distinct Aspects of Coupling between Gαi and GIRK Channel Revealed by Fluorescently-Labeled Gαi3 Subunits. J Biol Chem 286, 33223-33235.
- Efendiev R and Dessauer CW. (2011) AKAPs and Adenylyl Cyclase in Cardiovascular Physiology and Pathology. J Cardio Pharm 58, 339-344.
- Efendiev, R, Samelson, BK, Nguyen, BT, Phatarpekar, PV, Baameur, F, Scott, JD, Dessauer, CW. (2010) AKAP79 interacts with multiple adenylyl cyclase (AC) isoforms and scaffolds AC 5 and 6 to AMPA receptors. J Biol Chem, 285(19):14450-8.
- Vayttaden SJ, Friedman J, Tran TM, Rich TC, Dessauer CW, and Clark RB. (2010). Quantitative Modeling of GRK-Mediated β2AR Regulation. PLoS Computational Biology 6, e1000647.
- Sadana R, Dascal N, and Dessauer, CW. N-terminus of Type 5 Adenylyl Cyclase Scaffolds Gs Heterotrimer. Mol Pharm, 76, 1256-1264, 2009.
- Sadana, R and Dessauer, CW. Physiological Roles for G-Protein Regulated Adenylyl Cyclase Isoforms: Insights from Knockout and Overexpression Studies. NeuroSignals, 17, 5-22, 2009.
- Dessauer CW. Adenylyl Cyclase – AKAP Complexes: The Next Dimension in cAMP Signaling. Mol Pharm, 76:935-941, 2009.
- Kapiloff, MA, Piggott, LA, Sadana, R, Li, J, Heredia, LA, Henson, E, Efendiev, R, and Dessauer, CW.: An adenylyl cyclase-mAKAPβ signaling complex maintains basal cAMP levels in cardiac myocytes. J Biol Chem, 284: 23540-23546, 2009
- Piggott, LA, Bauman, A, Scott, JD, and Dessauer, CW. The A-Kinase Anchoring Protein Yotiao Binds and Regulates Adenylyl Cyclase in Brain. Proc Natl Acad Sci, 105: 13835-13840, 2008
- Bauman, A, Soughayer, J, Nguyen, BT, Willoughby, D, Wong, W, Hoshi, N, Langeberg, LK, Cooper, DMF, Dessauer, CW, and Scott, JD. Dynamic regulation of cAMP synthesis through anchored PKA/Adenylyl cyclase V/VI complexes. Molecular Cell, 23(6): 925-931, 2006.
- Nguyen, BT and Dessauer, CW. Relaxin Stimulates PKCζ Translocation via PI3K to Increase cAMP Production in THP-1 Cells. Mol Endo, 19: 1012-1023, 2005.
- Chen-Goodspeed, M, Lukan, AN, and Dessauer, CW. Modeling of Gαi and Gαs Regulation by Human Types V and VI Adenylyl Cyclase. J Biol Chem., 280: 1808-1816, 2005.
- Salim, S, Sinnarajah, S, Kehrl, JH, and Dessauer, CW. Identification of RGS2 and Type V Adenylyl Cyclase Interaction Sites. J Biol Chem 278: 15842 – 15849, 2003.
- Nguyen, BT, Yang, L, Sanborn, BM, and Dessauer, CW. Phosphoinositide 3-Kinase Activity is Required for Biphasic Stimulation of cyclic AMP by Relaxin. Mol Endocrinol 17(6): 1075-84, 2003.
- Dessauer, CW, Chen-Goodspeed, M, and Chen, J. Mechanism of Gi-Mediated Inhibition of Type V Adenylyl Cyclase. J Biol Chem 277: 28823-28829, 2002.
- Sinnarajah, S, Dessauer, CW, Srikumar, D, Chen, J, Yuen, J, Yilman, S, Dennis, JC Morrison, EE, Vodyanoy, V, and Kehrl, JH. RGS2 Regulates Signal Transduction in Olfactory Neurons by Attenuating Adenylyl Cyclase III Activation. Nature 409: 1051-1055, 2001.