Calcium-dependent increases in protein kinase-A activity in mouse retinal ganglion cells are mediated by multiple adenylate cyclases.
Calcium-dependent increases in protein kinase-A activity in mouse retinal ganglion cells are mediated by multiple adenylate cyclases.
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DOI：
10.1371/journal.pone.0007877
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发表时间：
2009-11-17
期刊：
影响因子：
3.7
通讯作者：
Feller MB
中科院分区：
文献类型：
--
作者：
Dunn TA;Storm DR;Feller MB
神经元经历长期的、活动依赖的变化，这些变化是由第二信使级联激活所介导的。特别是，钙依赖激活的环-AMP/蛋白激酶A信号级联参与了几个发育过程，包括细胞存活、轴突生长和轴突细化。钙内流和cAMP/PKA途径激活之间的生化联系主要是通过腺苷环化酶介导的。本研究采用细胞内钙离子浓度和PKA活性的双重成像方法，研究了不同类型的钙依赖腺苷环化酶(Acs)在视网膜神经节细胞(RGCs)cAMP/PKA通路激活中的作用。令人惊讶的是，在缺乏AC1的无桶小鼠以及缺乏AC1和AC8的双基因敲除小鼠中，去极化诱导的钙依赖型PKA瞬时持续存在。AC1是RGC中主要的钙依赖型腺苷环化酶。此外，在RGC的一个子集中，去极化诱导的PKA瞬变在所有跨膜腺苷环化酶被抑制期间持续存在。这些结果与可溶性腺苷环化酶的存在相一致，该酶在神经元内cAMP/PKA级联的钙依赖激活中起作用。
Neurons undergo long term, activity dependent changes that are mediated by activation of second messenger cascades. In particular, calcium-dependent activation of the cyclic-AMP/Protein kinase A signaling cascade has been implicated in several developmental processes including cell survival, axonal outgrowth, and axonal refinement. The biochemical link between calcium influx and the activation of the cAMP/PKA pathway is primarily mediated through adenylate cyclases. Here, dual imaging of intracellular calcium concentration and PKA activity was used to assay the role of different classes of calcium-dependent adenylate cyclases (ACs) in the activation of the cAMP/PKA pathway in retinal ganglion cells (RGCs). Surprisingly, depolarization-induced calcium-dependent PKA transients persist in barrelless mice lacking AC1, the predominant calcium-dependent adenylate cyclase in RGCs, as well as in double knockout mice lacking both AC1 and AC8. Furthermore, in a subset of RGCs, depolarization-induced PKA transients persist during the inhibition of all transmembrane adenylate cyclases. These results are consistent with the existence of a soluble adenylate cyclase that plays a role in calcium-dependent activation of the cAMP/PKA cascade in neurons.
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DOI：
10.1073/pnas.0400050101
发表时间：
2004-03-02
影响因子：
11.1
作者：
Esposito, G;Jaiswal, BS;Gossen, JA
通讯作者：
Gossen, JA
影响因子：
5.3
作者：
Chandrasekaran, AR;Plas, DT;Crair, MC
通讯作者：
Crair, MC
影响因子：
2.9
作者：
CHOI, EJ;XIA, ZG;STORM, DR
通讯作者：
STORM, DR
影响因子：
5.3
作者：
Nicol, X;Muzerelle, A;Gaspar, P
通讯作者：
Gaspar, P
影响因子：
5.3
作者：
Chan, GCK;Tonegawa, S;Storm, DR
通讯作者：
Storm, DR