IDENTIFICATION OF INTEGRIN ALPHA(3)BETA-1 AS A NEURONAL THROMBOSPONDIN RECEPTOR MEDIATING NEURITE OUTGROWTH
IDENTIFICATION OF INTEGRIN ALPHA(3)BETA-1 AS A NEURONAL THROMBOSPONDIN RECEPTOR MEDIATING NEURITE OUTGROWTH
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DOI：
10.1016/0896-6273(95)90038-1
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发表时间：
1995-08-01
期刊：
影响因子：
16.2
通讯作者：
REICHARDT, LF
中科院分区：
文献类型：
--
作者：
DEFREITAS, MF;YOSHIDA, CK;REICHARDT, LF
血小板反应蛋白是细胞外基质蛋白家族，在整个发育中的神经系统中表达，可促进体外神经突生长，并帮助介导新生儿小脑外植体中颗粒细胞跨分子层的迁移。介导这些相互作用的受体之前尚未被鉴定。在这项研究中，针对整合素 α(3) β(1) 异二聚体产生的单克隆抗体显示可抑制大鼠交感神经元对血小板反应蛋白-1 的神经突生长。 α(3) beta(1)被发现在体外表达于交感神经元的细胞体、神经突和生长锥上，以及体内表达于穿过颈上神经节富含血小板反应蛋白的外鞘的交感轴突上，这与其介导轴突生长的作用一致。受体-配体结合测定用于证明免疫纯化的 α(3) beta(1) 与血小板反应蛋白-1 的直接结合。这些结果表明整合素α(3)β(1)和血小板反应蛋白-1之间存在直接相互作用，其在体外介导神经突生长，并且可能在体内介导相同的相互作用。
Thrombospondins are a family of extracellular matrix proteins expressed throughout the developing nervous system that promote neurite outgrowth in vitro and help mediate the migration of granule cells across the molecular layer in explants of neonatal cerebellum. The receptors mediating these interactions have not previously been identified. In this study, monoclonal antibodies raised to the integrin alpha(3) beta(1) heterodimer are shown to inhibit neurite outgrowth by rat sympathetic neurons on thrombospondin-1. alpha(3) beta(1) is found to be expressed on the cell body, neurites, and growth cones of sympathetic neurons in vitro and on sympathetic axons passing through the thrombospondin-rich outer sheath of the superior cervical ganglion in vivo, consistent with its role in mediating axon outgrowth. A receptor-ligand binding assay is used to demonstrate the direct binding of immunopurified alpha(3) beta(1) to thrombospondin-1. These results demonstrate a direct interaction between the integrin alpha(3) beta(1) and thrombospondin-1, which mediates neurite outgrowth in vitro and is likely to mediate the same interactions in vivo.