最新一期生物化学期刊 (Journal of Biological Chemistry)的一份研究报告指出，科学家找到了三个特殊的蛋白质，可以使成熟的脑神经细胞，神奇的延伸细胞的长度，比起平常的脑神经细胞来说，足足大了四倍到八倍之多。
据了解研究人员所发现的三个蛋白质 分别称为GPR3 、GPR6 和 GPR12，主导这个研究计划的 Yoshinaga Saeki博士表示，研究人员以大鼠 (Rat)的成熟脑细胞为实验的材料，在额外加入 GPR3、GPR6 和GPR12 这三个分子后，原本已经是属于成熟的脑神经细胞，开始快速的延伸生长，相对于对照组而言，就像是重复了三次的生长周期一般。
研究人员深入的分析，发现这三个分子的加入，都可以明显的活化了神经细胞里的 cAMP分子，而就过去的研究数据显示， cAMP分子在神经细胞的生长过程之中，扮演着关键性的角色，简单的说，已经成熟的神经细胞，透过了 GPR3、 GPR6 和 GPR12的刺激，再度启动了生长的能力，而延伸了原本的细胞长度。
科学家认为这是一个相当大的突破，因为就那些因为中风、外伤，因此造成脑部神经组织受到伤害的患者来说，可能透过这三个关键分子的发现，重建受伤的组织。
(资料来源 : Bio.com)
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Originally published In Press as doi:10.1074/jbc.M700911200 on February 6, 2007
J. Biol. Chem., Vol. 282, Issue 14, 10506-10515, April 6, 2007
Neural Expression of G Protein-coupled Receptors GPR3, GPR6, and GPR12 Up-regulates Cyclic AMP Levels and Promotes Neurite Outgrowth*
Shigeru Tanaka, Ken Ishii, Kazue Kasai, Sung Ok Yoon¶, and Yoshinaga Saeki1
From the Dardinger Laboratory for Neuro-oncology and Neurosciences, Department of Neurological Surgery, ¶Department of Molecular and Cellular Biochemistry, and Center for Molecular Neurobiology, the Ohio State University, Columbus, Ohio 43210 and the Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan
Cyclic AMP regulates multiple neuronal functions, including neurite outgrowth and axonal regeneration. GPR3, GPR6, and GPR12 make up a family of constitutively active G protein-coupled receptors (GPCRs) that share greater than 50% identity and 65% similarity at the amino acid level. They are highly expressed in the central nervous system, and their expression in various cell lines results in constitutive stimulation of cAMP production. When the constitutively active GPCRs were overexpressed in rat cerebellar granule neurons in culture, the transfected neurons exhibited significantly enhanced neurite outgrowth and overcame growth inhibition caused by myelin-associated glycoprotein. GPR12-mediated neurite outgrowth was the most prominent and was shown to depend on Gs and cAMP-dependent protein kinase. Moreover, the GPR12-mediated rescue from myelin-associated glycoprotein inhibition was attributable to cAMP-dependent protein kinase-mediated inhibition of the small GTPase, RhoA. Among the three receptors, GPR3 was revealed to be enriched in the developing rat cerebellar granule neurons. When the endogenous GPR3 was knocked down, significant reduction of neurite growth was observed, which was reversed by expression of either GPR3 or GPR12. Taken together, our results indicate that expression of the constitutively active GPCRs up-regulates cAMP production in neurons, stimulates neurite outgrowth, and counteracts myelin inhibition. Further characterization of the GPCRs in developing and injured mammalian neurons should provide insights into how basal cAMP levels are regulated in neurons and could establish a firm scientific foundation for applying receptor biology to treatment of various neurological disorders.
