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Nerve growth cone guidance mediated by G protein–coupled receptors

Nature Neuroscience volume 5, pages 843–848 (2002)Cite this article

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 Gi 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.

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Figure 1: Chemorepulsion of growth cones induced by a gradient of SDF-1 or baclofen.
Figure 2: The modulatory role of cyclic nucleotides.
Figure 3: Ca2+ signaling in cerebellar granule neurons triggered by SDF-1.
Figure 4: Dependence of GPCR-mediated turning on PLC–PKC/IP3 signaling pathways.
Figure 5: PKC activation by SDF-1 in cultured cerebellar granule cells.
Figure 6: Gradients of drugs that activate or inhibit PKC or inhibit IP3 receptors are sufficient to induce growth cone turning.

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Acknowledgements

This work was supported by grants from the Major State Basic Research Program of China and from the Shanghai Science and Technology Development Foundation.

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Authors and Affiliations

  1. Institute of Neuroscience, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, 320 Yue-yang Road, 200031, Shanghai, China

    Yang Xiang, Yan Li, Zhe Zhang, Kai Cui, Sheng Wang, Xiao-bing Yuan, Chien-ping Wu, Mu-ming Poo & Shumin Duan

  2. Division of Neurobiology, Department of Molecular and Cell Biology, University of California, Berkeley, 94720-3200, California, USA

    Mu-ming Poo

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Xiang, Y., Li, Y., Zhang, Z. et al. Nerve growth cone guidance mediated by G protein–coupled receptors. Nat Neurosci 5, 843–848 (2002). https://doi.org/10.1038/nn899

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