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首页> 外文会议>Meeting on Cell Signaling World: Signal Transduction Pathways as Therapeutic Targets >Activation and Endocytic Internalization of Melanocortin 3 Receptor in Neuronal Cells
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Activation and Endocytic Internalization of Melanocortin 3 Receptor in Neuronal Cells

机译：黑素皮质素3受体在神经元细胞中的激活和内在内在化。

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Melanocortins play a central role in autonomic modula tion of metabolism by acting through a family of highly homologous G protein-coupled receptors. Studies with gene knockout mice have impli cated neural melanocortin receptors, MC3R and MC4R, in the etiology of obesity, insulin resistance, and salt-sensitive hypertension. In an at tempt to better understand the mechanisms of function of these recep tors, we expressed MC3R and MC4R in neuronal cells and demonstrated their co-localization to several membrane regions. We now show that in cultured neuronal cells, MC3R localizes to lipid rafts and undergoes endocytic internalization upon activation by γ-MSH through a protein kinase-sensitive pathway. The appearance of the internalized receptor in lysosomes suggests that it is subsequently degraded. The expression of protein kinase A regulatory subunits and of c-Jun and c-Fos was analyzed by either immunoblotting or real-time PCR. No discernable changes were observed in the expression levels of these protein kinase A and protein ki nase C responsive genes. Immunohistochemical studies showed a robust expression of MC3R protein in brain nuclei with relevance to cardiovas cular function and fluid homeostasis further supporting the notion that the physiological effects of melanocortins on the cardiovascular system arise from effects on the central nervous system.
机译：黑色素皮质素通过一系列高度同源的G蛋白偶联受体发挥作用，在代谢的自主调节中发挥重要作用。基因敲除小鼠的研究在肥胖，胰岛素抵抗和盐敏感性高血压的病因中隐含了神经黑皮质素受体MC3R和MC4R。为了更好地理解这些受体的功能机制，我们尝试在神经元细胞中表达MC3R和MC4R，并证明它们共定位于几个膜区域。我们现在显示，在培养的神经元细胞中，MC3R定位于脂质筏，并在通过蛋白激酶敏感途径的γ-MSH激活后经历胞吞内在化。内在受体在溶酶体中的出现表明其随后被降解。通过免疫印迹或实时PCR分析蛋白激酶A调节亚基以及c-Jun和c-Fos的表达。这些蛋白激酶A和蛋白激酶C响应基因的表达水平未观察到明显的变化。免疫组织化学研究表明，MC3R蛋白在脑核中表达强健，与心血管功能和体液稳态有关，这进一步支持了黑皮质素对心血管系统的生理作用源自对中枢神经系统的影响这一观点。

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