RT Journal Article
SR Electronic
T1 Soluble Adenylyl Cyclase Activity Is Necessary for Retinal Ganglion Cell Survival and Axon Growth
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 7734
OP 7744
DO 10.1523/JNEUROSCI.5288-11.2012
VO 32
IS 22
A1 Raul G. Corredor
A1 Ephraim F. Trakhtenberg
A1 Wolfgang Pita-Thomas
A1 Xiaolu Jin
A1 Ying Hu
A1 Jeffrey L. Goldberg
YR 2012
UL http://www.jneurosci.org/content/32/22/7734.abstract
AB 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.