The hippocampal laminin matrix is dynamic and critical for neuronal survival
The hippocampal laminin matrix is dynamic and critical for neuronal survival
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DOI：
10.1091/mbc.e02-12-0832
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发表时间：
2003-07-01
影响因子：
3.3
通讯作者：
Strickland, S
中科院分区：
文献类型：
--
作者：
Chen, ZL;Indyk, JA;Strickland, S
层粘连蛋白是参与神经元发育、存活和再生的细胞外基质蛋白。在小鼠海马兴奋毒素刺激过程中，神经元与层粘连蛋白-10 （α 5, β 1, γ 1）的相互作用可防止神经元死亡。为了研究层粘连蛋白如何参与神经元活力，我们将层粘连蛋白-1 （alpha1,beta1,gamma1）注入小鼠海马。这种输注特别破坏了内源性层粘连蛋白层。这种破坏至少部分是由于层粘连蛋白-1 γ -1链与内源性层粘连蛋白-10的相互作用，因为抗层粘连蛋白γ -1抗体的输注具有相同的效果。层粘连蛋白-1对层粘连蛋白层的破坏不需要完整的蛋白，因为输注纤溶酶消化的层粘连蛋白-1也有类似的结果；2)是转录后的，因为对层粘连蛋白mRNA表达没有影响；3)在tPA（-/-）和纤溶酶原（-/-）小鼠中均发生，表明纤溶酶活性的增加与此无关。最后，尽管tPA（-/-）小鼠通常对兴奋毒素诱导的神经变性具有抗性，但内源性层粘连蛋白-1或抗层粘连蛋白γ -1抗体破坏内源性层粘连蛋白层，使tPA（-/-）海马神经元对海碱盐敏感。这些结果表明，神经元与沉积基质的相互作用不一定是与可溶性成分的相互作用，层粘连蛋白基质是一种动态结构，可被外源分子修饰。
Laminins are extracellular matrix proteins that participate in neuronal development, survival, and regeneration. During excitotoxin challenge in the mouse hippocampus, neuron interaction with laminin-10 (alpha5,beta1,gamma1) protects against neuronal death. To investigate how laminin is involved in neuronal viability, we infused laminin-1 (alpha1,beta1,gamma1) into the mouse hippocampus. This infusion specifically disrupted the endogenous laminin layer. This disruption was at least partially due to the interaction of the laminin-1 gamma1 chain with endogenous laminin-10, because infusion of anti-laminin gamma1 antibody had the same effect. The disruption of the laminin layer by laminin-1 1) did not require the intact protein because infusion of plasmin-digested laminin-1 gave similar results; 2) was posttranscriptional, because there was no effect on laminin mRNA expression; and 3) occurred in both tPA(-/-) and plasminogen(-/-) mice, indicating that increased plasmin activity was not responsible. Finally, although tPA(-/-) mice are normally resistant to excitotoxin-induced neurodegeneration, disruption of the endogenous laminin layer by laminin-1 or anti-laminin gamma1 antibody renders the tPA(-/-) hippocampal neurons sensitive to kainate. These results demonstrate that neuron interactions with the deposited matrix are not necessarily recapitulated by interactions with soluble components and that the laminin matrix is a dynamic structure amenable to modification by exogenous molecules.