Education

Ph.D.
Louisiana State University, 1993

Areas of Interests

Research Interests

Mechanisms of adenylyl cyclase regulation

Research Information

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 or regulation of pain responses.  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, kinases and other interacting 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 within dorsal root ganglia to control pain responses and also function in the heart to control contractile events.  We are currently using biochemical and functional studies in DRG neurons and heart to further define the nature of adenylyl cyclase complexes and to understand how specificity of signaling is generated and maintained under physiological and pathophysiological conditions.

LAB WEBSITE:   www.Dessauer-Lab.com

Publications

Publication Information

References

  • Baldwin TA, Li Y, Brand CS, Watts VJ and Dessauer CW.  (2019). Insights into the regulatory properties of human adenylyl cyclase type 9.  Mol Pharm, 95: 349-360.
  • Odem MA, Bavencoffe AG, Cassidy RM, Lopez ER, Tian J, Dessauer CW, Walters ET.  (2018).  Isolated Nociceptors Reveal Multiple Specializations for Generating Irregular Ongoing Activity Associated with Ongoing Pain. Pain, 159:2347-2362.
  • Gemma N, Cordomí A, Casadó-Anguera V, Moreno E, Cai NS, Cortés A, Canela EI, Dessauer CW, Casadó V, Pardo L, Lluís C, and Ferré S. (2018).  Functional pre-coupled complexes of receptor heteromers and adenylyl-cyclase. Nature Communications, 9(1):1242.
  • Baldwin TA and Dessauer CW.  (2018).  Function of Adenylyl Cyclase in Heart: the AKAP Connection.  J Cardiovasc Dev Dis 5(1), 2.
  • Luo J, Bavencoffe A, Yang P, Feng J, Yin S, Qian A, Yu W, Liu S, Gong X, Cai T, Walters ET, Dessauer CW, and Hu H. (2018).  Zinc inhibits TRPV1 to alleviate chemotherapy-induced neuropathic pain. J Neuroscience 38(2):474-483.
  • Li Y, Baldwin TA, Wang Y, Brand CS, and Dessauer CW. (2017). Deletion of type 9 adenylyl cyclase triggers diastolic dysfunction and decreased phosphorylation of heat shock protein 20. Scientific Reports, 7(1):5522.
  • Dessauer CW, Watts VJ, Ostrom RS, Conti M, Dove S and Seifert R.  (2017).  IUPHAR: Mammalian adenylyl cyclases: From structure to small molecule modulators. Pharmacological Reviews 69(2):93-139.
  • Dessauer, CW. (2017).  Shining a Light on GPCR Complexes. J Biol Chem, 292(34):14290-14291.
  • Brust TF, Alongkronrusmee D, Soto-Velasquez M, Baldwin TA, Ye Z, Dai M, Dessauer CW, van Rijn RM, Watts VJ.  (2017).  A small molecule inhibitor of type 1 adenylyl cyclase activity as a non-opioid analgesic agent. Sci Signaling, 10(467), eaah6381.
  • Bavencoffe A, Li Y, Wu Z, Qang Y, Herrera J, Kennedy EJ, Walters ET, and Dessauer CW. (2016).  Persistent Electrical Activity in Primary Nociceptors after Spinal Cord Injury Is Maintained by Scaffolded Adenylyl Cyclase and Protein Kinase A and Associated with Altered Adenylyl Cyclase Regulation. J Neuroscience, 36(5):1660-8.
  • Brand CS, Sadana R, Malik S, Smrcka AV, Dessauer CW.  (2015).  Adenylyl Cyclase 5 Regulation by Gβγ Involves Isoform Specific Use of Multiple Interaction Sites. Mol Pharm, 88(4):758-67.
  • Xie K, Masuho I, Shih CC, Cao Y, Sasaki K, Lai CW, Han PL, Ueda H, Dessauer CW, Ehrlich ME, Xu B, Willardson BM and Martemyanov KA.  (2015).  Stable G protein-effector in striatal neurons: mechanism of assembly and role in neurotransmitter signaling. eLife, 10.7554/eLife.10451.
  • Li Y and Dessauer CW: Identi0fying Complexes of Adenylyl Cyclase with A-kinase Anchoring Proteins.  (2015).  In X. Cheng Editor, Cyclic Nucleotide Signaling. CRC Press, a Taylor and Francis Company, Boca Raton, FL. ISBN: 978-1-4822-3556-2.
  • Dvir M, Strulovich R, Sachyani D, Cohen IB, Haitin Y, Dessauer CW, Pongs O, Kass RS, 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 CW, 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 IF, Tsemakhovich V, Rishal I, Dessauer CW, 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 CS, Hocker HJ, Gorfe AA, Cavasotto CN, Dessauer CW. (2013).  Isoform selectivity of adenylyl cyclase inhibitors: characterization of known and novel compounds. J Pharmacol Exp Ther. 347(2): 265-75.
  • Conley JM, Brand CS, Bogard AS, Pratt EPS, Xu R, Hockerman GH, Ostrom R, Dessauer CW, and Watts VJ. (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 MX, Dessauer CW. (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 Rev Pharm and Tox., 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 adenylyl 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. (2009). Physiological Roles for G-Protein Regulated Adenylyl Cyclase Isoforms: Insights from Knockout and Overexpression Studies. NeuroSignals, 17, 5-22.
  • Dessauer CW. (2009). Adenylyl Cyclase – AKAP Complexes: The Next Dimension in cAMP Signaling. Mol Pharm, 76:935-941.
  • Kapiloff MA, Piggott LA, Sadana R, Li J, Heredia LA, Henson E, Efendiev R, and Dessauer CW. (2009). An adenylyl cyclase-mAKAPβ signaling complex maintains basal cAMP levels in cardiac myocytes. J Biol Chem., 284: 23540-23546.
  • Piggott LA, Bauman A, Scott JD, and Dessauer CW. (2008). The A-Kinase Anchoring Protein Yotiao Binds and Regulates Adenylyl Cyclase in Brain. Proc Natl Acad Sci, 105: 13835-13840.
  • Bauman A, Soughayer J, Nguyen BT, Willoughby D, Wong W, Hoshi N, Langeberg LK, Cooper DMF, Dessauer CW, and Scott JD. (2006) Dynamic regulation of cAMP synthesis through anchored PKA/Adenylyl cyclase V/VI complexes.  Molecular Cell, 23(6): 925-931.
  • Nguyen BT, and Dessauer CW. (2005). Relaxin Stimulates PKCζ Translocation via PI3K to Increase cAMP Production in THP-1 Cells.  Mol Endo, 19: 1012-1023.
  • Chen-Goodspeed M, Lukan AN, and Dessauer CW. (2005). Modeling of Gαi and Gαs Regulation by Human Types V and VI Adenylyl Cyclase.  J Biol Chem., 280: 1808-1816.
  • Salim S, Sinnarajah S, Kehrl JH, and Dessauer CW. (2003). Identification of RGS2 and Type V Adenylyl Cyclase Interaction Sites. J Biol Chem 278: 15842 – 15849.
  • Nguyen BT, Yang L, Sanborn BM, and Dessauer CW. (2003). Phosphoinositide 3-Kinase Activity is Required for Biphasic Stimulation of cyclic AMP by Relaxin. Mol Endocrinol 17(6): 1075-84.
  • Dessauer CW, Chen-Goodspeed M, and Chen J. (2002). Mechanism of Gi-Mediated Inhibition of Type V Adenylyl Cyclase. J Biol Chem 277: 28823-28829.
  • Sinnarajah S, Dessauer CW, Srikumar D, Chen J, Yuen J, Yilman S, Dennis JC, Morrison EE, Vodyanoy V, and Kehrl JH. (2001). RGS2 Regulates Signal Transduction in Olfactory Neurons by Attenuating Adenylyl Cyclase III Activation. Nature 409: 1051-1055.