Soluble adenylyl cyclase activity is necessary for retinal ganglion cell survival and axon growth.
Soluble adenylyl cyclase activity is necessary for retinal ganglion cell survival and axon growth.
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DOI：
10.1523/jneurosci.5288-11.2012
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发表时间：
2012-05-30
期刊：
影响因子：
--
通讯作者：
Goldberg JL
中科院分区：
文献类型：
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作者：
Corredor RG;Trakhtenberg EF;Pita-Thomas W;Jin X;Hu Y;Goldberg JL
环磷酸腺苷（cAMP）是一种重要的第二信使介导的活动依赖性神经元的存活和轴突生长。本实验研究了可溶性腺苷酸环化酶（sAC，ADCY 10）在中枢神经系统视网膜神经节细胞（RGCs）中的表达及功能。我们发现sAC蛋白表达于多个RGC区室，包括细胞核、细胞质和轴突。sAC活化使cAMP增加到高于跨膜腺苷酸环化酶（tmAC）活化所见的水平。电活动和碳酸氢盐，生理sAC激活剂，显着增加生存和轴突生长，而药理学或siRNA介导的sAC抑制显着降低RGC的生存和轴突生长在体外，和生存在体内。相反，在AC 1/AC 8双敲除小鼠或特异性抑制tmACs后的RGC中，RGC存活和轴突生长没有改变。这些数据确定了一种新的sAC介导的cAMP信号通路调节RGC的生存和轴突生长，并提出了新的神经保护或再生策略的基础上sAC调制。
Cyclic adenosine monophosphate (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 central nervous system (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 was unaltered in RGCs from AC1/AC8 double knockout 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.