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Title: G蛋白耦联受体介导的神经生长锥导向
Author: 相杨
Degree Level: 博士
Issued Date: 2003
Degree Grantor: 中国科学院神经科学研究所
Place of Degree Grantor: 中国科学院神经科学研究所
Supervisor: 蒲慕明
Keyword: G蛋白祸联受体 ; 生长锥导向
Alternative Title: Nerve growth cone guidance mediated by G protein-coupled receptors
Abstract: 发育中神经元的生长锥能够在导向因子浓度梯度的指导下发生偏转,帮助轴突或树突找到它们正确的靶细胞。以前的证据表明,SDF-1,一种经典的chemokine,能够吸引白细胞和迁移中的神经元,这种作用是通过G蛋白祸联受体介导的。利用生长锥转向分析,我们发现SDF-1的浓度梯度能够吸引或排斥培养的小脑颗粒细胞的生长锥。同样的,GABAB受体的激动剂boclofen的浓度梯度也能够吸引或排斥爪蟾脊髓神经元的生长锥。信号转导机制的研究表明,SDF-1和baclofen激活了生长锥表面的G蛋白祸联受体,通过Gi将信号传递给PLC,进而激活PKC和IP3信号通路。通常条件下,PKC通路介导了生长锥排斥反应,而IP3通路介导了吸引反应,由于PKC通路占据主导,SDF一1和baclofen排斥生长锥。升高胞内cGMP水平后,PKC通路和IP3通路均介导了吸引反应,SDF一1和baclofen吸引生长锥。因此,G蛋白祸联受体可以介导生长锥的吸引或 排斥反应,并且chemokine也能作为导向因子指导生长锥转向。
English Abstract: Growing axons navigate by responding to chemical guidance cues. Here we report that growth cones of rat cerebellar axons in culture turned away from a gradient of SDF-1, a chemokine that attracts migrating leukocytes and cerebellar granule cells via a G protein-coupled receptor (GPCR). Similarly, Xenopus spinal growth cones turned away from a gradient of baclofen, an agonist of the GABAB receptor. This response was mediated by G; and subsequent activation of phospholipase C (PLC), which triggered two pathways: protein kinase C (PKC) led to repulsion, and inositol 1,4,5-triphosphate (IP3) receptor activation led to attractive turning. Under normal culture conditions, PKC-dependent repulsion dominated, but the repulsion could be converted to attraction by inhibiting PKC or by elevating cytosolic cGMP. Thus, GPCRs can mediate both repulsive and attractive axon guidance in vitro, and chemokines may serve as guidance cues for axon pathfinding.
Language: 中文
Content Type: 学位论文
URI: http://ir.sibs.ac.cn/handle/331001/2254
Appears in Collections:神经所(总)_学位论文

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Recommended Citation:
G蛋白耦联受体介导的神经生长锥导向.相杨[d].中国科学院神经科学研究所,2003.20-25
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