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Galectin-1/β1 整合素相互作用对成年神经祖细胞的调控。

Regulation of adult neural progenitor cells by Galectin-1/beta1 Integrin interaction.

机构信息

Department of Physiology, Keio University School of Medicine, Tokyo, Japan.

出版信息

J Neurochem. 2010 Jun;113(6):1516-24. doi: 10.1111/j.1471-4159.2010.06712.x. Epub 2010 Mar 29.

Abstract

Neural stem cells (NSCs) proliferate and generate new neurons in the adult brain. A carbohydrate-binding protein (lectin), Galectin-1, is expressed in the NSCs in the subependymal zone (SEZ) of the adult mouse brain. The infusion and knockout of Galectin-1 in the SEZ results in an increase and decrease, respectively, of NSCs and subsequently born progenitor cells. The molecular mechanism of this effect, however, has been unknown. Previous studies outside the brain suggest that Galectin-1 binds to a carbohydrate structure of beta1 Integrin and modulates cell adhesion. Here, we studied the functional interaction between Galectin-1 and beta1 Integrin in the adult mouse SEZ. Beta1 Integrin was purified from adult SEZ tissue by binding to a Galectin-1 affinity column, and this binding depended on Galectin-1's carbohydrate-binding activity. In adult brain sections, Galectin-1-binding activity was detected on beta1 Integrin-expressing cells in the SEZ. Furthermore, in the adult SEZ, the simultaneous infusion of a beta1 Integrin-neutralizing antibody with Galectin-1 protein reversed the increasing effect of Galectin-1 on the number of adult neural progenitor cells (NPCs). Finally, intact beta1 Integrin was required for Galectin-1's function in NPC adhesion in vitro. These results suggest that the interaction between beta1 Integrin and Galectin-1 plays an important role in regulating the number of adult NPCs through mechanisms including cell adhesion.

摘要

神经干细胞(NSCs)在成人大脑中增殖并产生新的神经元。一种碳水化合物结合蛋白(凝集素)Galectin-1 在成年鼠脑室下区(SEZ)的 NSCs 中表达。SEZ 中 Galectin-1 的输注和敲除分别导致 NSCs 和随后产生的祖细胞增加和减少。然而,这种效应的分子机制尚不清楚。大脑以外的先前研究表明,Galectin-1 与 beta1 整合素的碳水化合物结构结合并调节细胞黏附。在这里,我们研究了成年鼠 SEZ 中 Galectin-1 和 beta1 整合素之间的功能相互作用。通过结合 Galectin-1 亲和柱从成年 SEZ 组织中纯化 beta1 整合素,并且这种结合依赖于 Galectin-1 的碳水化合物结合活性。在成年脑切片中,Galectin-1 结合活性在 SEZ 中表达 beta1 整合素的细胞上检测到。此外,在成年 SEZ 中,同时输注 beta1 整合素中和抗体与 Galectin-1 蛋白可逆转 Galectin-1 对成年神经祖细胞(NPCs)数量的增加作用。最后,完整的 beta1 整合素是 Galectin-1 在体外 NPC 黏附中发挥作用所必需的。这些结果表明,beta1 整合素和 Galectin-1 之间的相互作用通过包括细胞黏附在内的机制在调节成年 NPC 数量方面发挥着重要作用。

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