The long term objective of this proposal is to elucidate the mechanisms for regulation of brain adenylate cyclase by calmodulin (CaM) and the cAMP dependent protein kinase. Recent data from this laboratory using azido[125I]CaM and partially purified adenylate cyclase have implicated a 150,000 dalton polypeptide as the catalytic subunit of the CaM sensitive adenylate cyclase from bovine cerebral cortex. This polypeptide has been isolated in quantity by preparative SDS gel electrophoresis and shown to elicit polyclonal anti-cyclase antibodies with rabbits. We have also discovered that the catalytic subunit of protein kinase inhibits the activity of the CaM sensitive adenylate cyclase in the presence of ATP. It is our working hypothesis that direct phosphorylation of this adenylate cyclase may inhibit enzyme activity.
The specific aims of this project include further purification of the CaM sensitive adenylate cyclase, preparation of monoclonal and polyclonal antibodies against specific polypeptides in the preparation, and elucidation of the quaternary structure of the enzyme complex. In addition, the significance of protein kinase inhibition of the enzyme will be evaluated.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Biochemistry Study Section (BIO)
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University of Washington
Schools of Medicine
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Luo, Jie; Chen, Xuanmao; Pan, Yung-Wei et al. (2015) The type 3 adenylyl cyclase is required for the survival and maturation of newly generated granule cells in the olfactory bulb. PLoS One 10:e0122057
Wardlaw, Sarah M; Phan, Trongha X; Saraf, Amit et al. (2014) Genetic disruption of the core circadian clock impairs hippocampus-dependent memory. Learn Mem 21:417-23
Wang, Wenbin; Pan, Yung-Wei; Zou, Junhui et al. (2014) Genetic activation of ERK5 MAP kinase enhances adult neurogenesis and extends hippocampus-dependent long-term memory. J Neurosci 34:2130-47
Chen, Ying-Zhang; Friedman, Jennifer R; Chen, Dong-Hui et al. (2014) Gain-of-function ADCY5 mutations in familial dyskinesia with facial myokymia. Ann Neurol 75:542-9
Saraf, Amit; Luo, Jie; Morris, David R et al. (2014) Phosphorylation of eukaryotic translation initiation factor 4E and eukaryotic translation initiation factor 4E-binding protein (4EBP) and their upstream signaling components undergo diurnal oscillation in the mouse hippocampus: implications for memory per J Biol Chem 289:20129-38
Luo, Jie; Phan, Trongha X; Yang, Yimei et al. (2013) Increases in cAMP, MAPK activity, and CREB phosphorylation during REM sleep: implications for REM sleep and memory consolidation. J Neurosci 33:6460-8
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Pan, Yung-Wei; Storm, Daniel R; Xia, Zhengui (2013) Role of adult neurogenesis in hippocampus-dependent memory, contextual fear extinction and remote contextual memory: new insights from ERK5 MAP kinase. Neurobiol Learn Mem 105:81-92
Chen, Xuanmao; Xia, Zhengui; Storm, Daniel R (2012) Stimulation of electro-olfactogram responses in the main olfactory epithelia by airflow depends on the type 3 adenylyl cyclase. J Neurosci 32:15769-78
Pan, Yung-Wei; Chan, Guy C K; Kuo, Chay T et al. (2012) Inhibition of adult neurogenesis by inducible and targeted deletion of ERK5 mitogen-activated protein kinase specifically in adult neurogenic regions impairs contextual fear extinction and remote fear memory. J Neurosci 32:6444-55

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