Farwell A P, Tranter M P, Leonard J L
Molecular Endocrinology Laboratory, University of Massachusetts Medical School, Worcester 01655, USA.
Endocrinology. 1995 Sep;136(9):3909-15. doi: 10.1210/endo.136.9.7649099.
Adhesive interactions among the extracellular matrix protein laminin, cell surface receptors known as integrins, and the microfilament network play a fundamental role in the regulation of neural cell migration during brain development. The disturbed neuronal migration that occurs when thyroid hormone is lacking during early neonatal life contributes to the profound morphological alterations characteristic of the cretinous brain. We have previously shown that thyroid hormone determines the organization of the microfilament network in astrocytes by regulating the polymerization of F-actin fibers. In this paper, we examined whether T4-dependent alterations in microfilament organization affected astrocyte-laminin interactions. We show that T4-treated astrocytes readily attached to laminin, whereas attachment of thyroid hormone-deficient cells to laminin was delayed. T4-dependent cell attachment to laminin was completely abolished by blocking integrin recognition sites with site-specific peptides or by depolymerizing the microfilaments with dihydrocytochalasin B. We also show that T4 was required for integrin clustering and focal contact formation in astrocytes attached to laminin. Thus, T4 dynamically regulates interactions between integrins and laminin via modulation of microfilament organization in astrocytes. The T4-dependent regulation of laminin-integrin interactions provides a mechanism by which this morphogenic hormone can influence neuronal migration and development.
细胞外基质蛋白层粘连蛋白、被称为整合素的细胞表面受体以及微丝网络之间的黏附相互作用，在大脑发育过程中神经细胞迁移的调节中起着基础性作用。新生儿早期缺乏甲状腺激素时发生的神经元迁移紊乱，会导致克汀病大脑特有的深刻形态学改变。我们之前已经表明，甲状腺激素通过调节F-肌动蛋白纤维的聚合来决定星形胶质细胞中微丝网络的组织。在本文中，我们研究了微丝组织中依赖于T4的改变是否影响星形胶质细胞与层粘连蛋白的相互作用。我们发现，经T4处理的星形胶质细胞很容易附着在层粘连蛋白上，而甲状腺激素缺乏的细胞与层粘连蛋白的附着则延迟。用位点特异性肽阻断整合素识别位点或用二氢细胞松弛素B使微丝解聚，可完全消除T4依赖的细胞与层粘连蛋白的附着。我们还表明，T4是附着在层粘连蛋白上的星形胶质细胞中整合素聚集和粘着斑形成所必需的。因此，T4通过调节星形胶质细胞中的微丝组织来动态调节整合素与层粘连蛋白之间的相互作用。T4对层粘连蛋白-整合素相互作用的依赖性调节提供了一种机制，通过这种机制，这种形态发生激素可以影响神经元的迁移和发育。
