Semaphorin 3A inhibits growth of adult sympathetic and parasympathetic neurones via distinct cyclic nucleotide signalling pathways
Semaphorin 3A inhibits growth of adult sympathetic and parasympathetic neurones via distinct cyclic nucleotide signalling pathways
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DOI：
10.1111/j.1476-5381.2010.01108.x
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发表时间：
2011-03-01
影响因子：
7.3
通讯作者：
Keast, J. R.
中科院分区：
文献类型：
--
作者：
Nangle, M. R.;Keast, J. R.
背景与目的emaphorin 3A （Sema3A）是许多发育中的神经元的重要分泌性排斥引导因子。Sema3A在成年期继续表达，其受体neuropilin-1 （Nrp-1）的表达可因神经损伤而改变。支配盆腔脏器的自主神经元在盆腔手术过程中特别容易受到损伤，交感神经和副交感神经再生失败或异常生长导致器官功能障碍。然而，尚不清楚成人骨盆神经元是否是Sema3A的潜在靶点。实验方法：采用生长锥塌陷法，在培养的成年大鼠盆腔神经节神经元中评估Sema3A和环核苷酸信号激活或抑制的作用。关键结果sema3a可引起表达Nrp-1的副交感神经细胞和交感神经细胞的生长锥塌陷。然而，Sema3A的作用是由每种神经元类型中不同的环核苷酸信号通路介导的。在副交感神经细胞中，生长锥塌陷需要cAMP和下游蛋白激酶A的激活。在交感神经元中，cGMP是sema3a诱导的崩溃所必需的；cAMP也会导致崩溃，但不是必需的。sema3a介导的cgmp依赖性交感神经元崩溃可能需要激活环核苷酸门控离子通道（CNGCs）。我们认为Sema3A是成人盆腔自主神经元的重要引导因子，操纵其独特的信号机制可能促进功能选择性再生或减弱异常生长。据我们所知，这也是第一个涉及CNGCs调节成年神经元生长锥动力学的研究。
BACKGROUND AND PURPOSESemaphorin 3A (Sema3A) is an important secreted repulsive guidance factor for many developing neurones. Sema3A continues to be expressed in adulthood, and expression of its receptor, neuropilin-1 (Nrp-1), can be altered by nerve injury. Autonomic neurones innervating the pelvic viscera are particularly susceptible to damage during pelvic surgical procedures, and failure to regenerate or aberrant growth of sympathetic and parasympathetic nerves lead to organ dysfunction. However, it is not known if adult pelvic neurones are potential targets for Sema3A.EXPERIMENTAL APPROACHThe effects of Sema3A and activation or inhibition of cyclic nucleotide signalling were assessed in adult rat pelvic ganglion neurones in culture using a growth cone collapse assay.KEY RESULTSSema3A caused growth cone collapse in both parasympathetic and sympathetic neurones expressing Nrp-1. However, the effect of Sema3A was mediated by distinct cyclic nucleotide signalling pathways in each neurone type. In parasympathetic neurones, cAMP and downstream activation of protein kinase A were required for growth cone collapse. In sympathetic neurones, cGMP was required for Sema3A-induced collapse; cAMP can also cause collapse but was not required. Sema3A-mediated, cGMP-dependent collapse in sympathetic neurones may require activation of cyclic nucleotide-gated ion channels (CNGCs).CONCLUSIONS AND IMPLICATIONSWe propose that Sema3A is an important guidance factor for adult pelvic autonomic neurones, and that manipulation of their distinct signalling mechanisms could potentially promote functional selective regeneration or attenuate aberrant growth. To our knowledge, this is also the first study to implicate CNGCs in regulating growth cone dynamics of adult neurones.