The role of matrix metalloproteinases in the morphogenesis of the cerebellar cortex
The role of matrix metalloproteinases in the morphogenesis of the cerebellar cortex
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DOI：
10.1080/14734220500247646
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发表时间：
2005-01-01
期刊：
影响因子：
3.5
通讯作者：
Luo, J
中科院分区：
文献类型：
--
作者：
Luo, J
小脑皮质的形态发生依赖于内在的遗传程序以及协调的细胞-细胞/细胞-细胞外基质(ECM)相互作用。基质金属蛋白酶家族由20多个成员组成，催化细胞外基质中所有蛋白质成分的降解。这些蛋白水解性内肽酶通过重塑ECM和调节膜相关受体的活性来调节细胞-细胞/细胞-ECM的相互作用。金属蛋白酶组织抑制因子(TIMPs)对MMPs的活性具有负性调控作用。MMPs和TIMP调节多种神经元功能，包括迁移、突起延伸和突触可塑性。MMP2、MMP3、MMP9、膜型MMP5、TIMP-1、TIMP-2和TIMP-3在小脑发育过程中均有表达。这些酶的表达/活性的时空模式表明，它们在小脑皮质的发育中发挥作用。用特定的抑制剂或封闭抗体阻断基质金属蛋白酶-2/-9的活性，以及利用基质金属蛋白酶-9基因敲除的小鼠，清楚地证实了基质金属蛋白酶-2/-9参与了小脑的形态发生的调节。讨论了这些酶对颗粒神经元迁移、浦肯野细胞树突形成和突触形成的潜在贡献。
The morphogenesis of the cerebellar cortex depends on intrinsic genetic programs as well as orchestrated cell-cell/ cell-extracellular matrix (ECM) interactions. The matrix metalloproteinase (MMP) family comprises of more than 20 members that catalyze the degradation of all the protein constituents of the ECM. These proteolytic endopeptidases mediate cell-cell/cell-ECM interactions by remodeling the ECM and modulating the activity of membrane-associated receptors. The activity of MMPs is negatively controlled by the tissue inhibitors of metalloproteinases (TIMPs). The MMPs and TIMPs regulate diverse neuronal functions including migration, process extension and synaptic plasticity. MMP-2, -3, -9, membrane type 5-MMP (MT5-MMP), TIMP-1, -2 and -3 are expressed in the developing cerebellum. The spatiotemporal pattern of expression/activity of these enzymes suggests that they play a role in the development of the cerebellar cortex. Blockage of MMP-2/-9 activity by specific inhibitors or blocking antibody, as well as using MMP-9 knock-out mice, clearly establishes that MMP-2/-9 participates in the regulation of morphogenesis of the cerebellum. The potential contributions of these enzymes to granule neuron migration, Purkinje cell dendritogenesis and synaptogenesis are discussed.