Gonthier B, Nasarre C, Roth L, Perraut M, Thomasset N, Roussel G, Aunis D, Bagnard D
INSERM U575, Physiopathologie du Système Nerveux, Centre de Neurochimie, 67084 Strasbourg, France.
Cereb Cortex. 2007 Jul;17(7):1712-21. doi: 10.1093/cercor/bhl082. Epub 2006 Oct 4.
In the developing cortex, axons and dendrites extend progressively in response to environmental cues attracting or repelling growing processes. Recent evidence suggests the existence of a functional link between guidance molecules and metalloproteinases. Here, we analyzed the putative functional interaction of matrix metalloproteinases (MMPs) with guidance cues of the semaphorin family during growth and guidance of cortical axons. Our results demonstrate that the expression pattern and the proteolytic activity of MMP-3 are consistent with a role of this particular MMP during cortical axon outgrowth. We found that MMP-3 is required for an optimal axon extension and is involved in the Sema3C-dependent chemoattraction of cortical axons by modulating both the growth capacity and the orientation of growth. Interestingly, the inhibitory Sema3A decreased both the expression and activity of MMP-3. Taken together, our results reveal a molecular interaction between MMPs and semaphorins providing new insight into the molecular mechanism allowing axonal growth cone to respond to environmental guidance cues in the context of cortical development.
在发育中的皮质中，轴突和树突会根据吸引或排斥生长过程的环境线索逐渐延伸。最近的证据表明，导向分子与金属蛋白酶之间存在功能联系。在这里，我们分析了基质金属蛋白酶（MMPs）与信号素家族的导向线索在皮质轴突生长和导向过程中的假定功能相互作用。我们的结果表明，MMP-3的表达模式和蛋白水解活性与这种特定的MMP在皮质轴突生长过程中的作用一致。我们发现，MMP-3是最佳轴突延伸所必需的，并且通过调节生长能力和生长方向参与Sema3C依赖的皮质轴突化学吸引。有趣的是，抑制性信号素Sema3A降低了MMP-3的表达和活性。综上所述，我们的结果揭示了MMPs与信号素之间的分子相互作用，为轴突生长锥在皮质发育背景下对环境导向线索作出反应的分子机制提供了新的见解。
