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Publication : Soluble adenylyl cyclase activity is necessary for retinal ganglion cell survival and axon growth.

First Author  Corredor RG Year  2012
Journal  J Neurosci Volume  32
Issue  22 Pages  7734-44
PubMed ID  22649251 Mgi Jnum  J:185199
Mgi Id  MGI:5427757 Doi  10.1523/JNEUROSCI.5288-11.2012
Citation  Corredor RG, et al. (2012) Soluble adenylyl cyclase activity is necessary for retinal ganglion cell survival and axon growth. J Neurosci 32(22):7734-44
abstractText  cAMP is a critical second messenger mediating activity-dependent neuronal survival and neurite growth. We investigated the expression and function of the soluble adenylyl cyclase (sAC, ADCY10) in CNS retinal ganglion cells (RGCs). We found sAC protein expressed in multiple RGC compartments including the nucleus, cytoplasm and axons. sAC activation increased cAMP above the level seen with transmembrane adenylate cyclase (tmAC) activation. Electrical activity and bicarbonate, both physiologic sAC activators, significantly increased survival and axon growth, whereas pharmacologic or siRNA-mediated sAC inhibition dramatically decreased RGC survival and axon growth in vitro, and survival in vivo. Conversely, RGC survival and axon growth were unaltered in RGCs from AC1/AC8 double knock-out mice or after specifically inhibiting tmACs. These data identify a novel sAC-mediated cAMP signaling pathway regulating RGC survival and axon growth, and suggest new neuroprotective or regenerative strategies based on sAC modulation.
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