Department of Physiology and The Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, Shanghai 200433, PR China.
Mol Cell Endocrinol. 2012 Oct 15;362(1-2):157-64. doi: 10.1016/j.mce.2012.06.003. Epub 2012 Jun 12.
Corticotropin-releasing hormone (CRH) has been shown to modulate dendritic development in hippocampus. Mitotic kinesin-like protein 1 (MKLP1) plays key roles in dendritic differentiation. In the present study, we examined the effects of CRH on MKLP1 expression in cultured hippocampal neurons and determine subsequent signaling pathways involved. CRH dose-dependently increased MKLP1 mRNA and protein expression. This effect can be reversed by CRHR1 antagonist but not by CRHR2 antagonist. CRHR1 knockdown impaired this effect of CRH. CRH stimulated GTP-bound Gαs protein and phosphorylated phospholipase C (PLC)-β3 expression, which were blocked by CRHR1 antagonist. Transfection of GP antagonist-2A, an inhibitory peptide of Gαq protein, blocked CRH-induced phosphorylated PLC-β3 expression. PLC and PKC inhibitors completely blocked whereas adenylyl cyclase (AC) and PKA inhibitors did not affect CRH-induced MKLP1 expression. Our results indicate that CRH act on CRHR1 to induce MKLP1 expression via PLC/PKC signaling pathway. CRH may regulate MKLP1 expression, thereby modulating dendritic development.
促肾上腺皮质释放激素（CRH）已被证明可调节海马中的树突发育。有丝分裂驱动蛋白样蛋白 1（MKLP1）在树突分化中发挥关键作用。在本研究中，我们研究了 CRH 对培养的海马神经元中 MKLP1 表达的影响，并确定了涉及的后续信号通路。CRH 呈剂量依赖性增加 MKLP1 mRNA 和蛋白表达。这种作用可以被 CRHR1 拮抗剂逆转，但不能被 CRHR2 拮抗剂逆转。CRHR1 敲低削弱了 CRH 的这种作用。CRH 刺激 GTP 结合的 Gαs 蛋白和磷酸化磷酯酶 C（PLC）-β3 的表达，这被 CRHR1 拮抗剂阻断。GP 拮抗剂-2A（Gαq 蛋白的抑制肽）的转染阻断了 CRH 诱导的磷酸化 PLC-β3 表达。PLC 和 PKC 抑制剂完全阻断，而腺苷酸环化酶（AC）和 PKA 抑制剂不影响 CRH 诱导的 MKLP1 表达。我们的结果表明，CRH 通过 CRHR1 作用于 CRHR1，通过 PLC/PKC 信号通路诱导 MKLP1 表达。CRH 可能调节 MKLP1 的表达，从而调节树突发育。
