神经突
细胞周期蛋白依赖激酶5
MAPK/ERK通路
细胞生物学
生物
信号转导
受体
兴奋剂
神经科学
蛋白激酶C
生物化学
丝裂原活化蛋白激酶激酶
体外
作者
Luisa Speranza,Angela Chambery,Marina Di Domenico,Marianna Crispino,Valeria Severino,Floriana Volpicelli,Marcello Leopoldo,Gian Carlo Bellenchi,Umberto di Porzio,Carla Perrone-Capano
标识
DOI:10.1016/j.neuropharm.2012.10.026
摘要
Serotonergic neurotransmission is mediated by at least 14 subtypes of 5-HT receptors. Among these, the CNS serotonin receptor 7 (5-HTR7) is involved in diverse physiological processes. Here we show that treatment of murine striatal and cortical neuronal cultures with 5-HTR7 agonists (8-OH-DPAT and LP-211) significantly enhances neurite outgrowth. This effect is abolished by the selective 5-HTR7 antagonist SB-269970, by the ERK inhibitor U0126, by the cyclin-dependent kinase 5 (Cdk5) inhibitor roscovitine, as well as by cycloheximide, an inhibitor of protein synthesis. These data indicate that 5-HTR7 activation stimulates extensive neurite elongation in CNS primary cultures, subserved by ERK and Cdk5 activation, and de novo protein synthesis. Two-dimensional (2D) gel electrophoresis coupled to Western blot analyses reveals both qualitative and quantitative expression changes in selected cytoskeletal proteins, following treatment of striatal primary cultures with LP-211. In particular, the 34 kDa isoform of MAP1B is selectively expressed in stimulated cultures, consistent with a role of this protein in tubulin polymerization and neurite elongation. In summary, our results show that agonist-dependent activation of the endogenous 5-HTR7 in CNS neuronal primary cultures stimulates ERK- and Cdk5-dependent neurite outgrowth, sustained by modifications of cytoskeletal proteins. These data support the hypothesis that the 5-HTR7 might play a crucial role in shaping neuronal morphology and behaviorally relevant neuronal networks, paving the way to new approaches able to modulate CNS connectivity.
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