Dunkle Erin Tolhurst, Zaucke Frank, Clegg Dennis O
Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106, USA.
Exp Eye Res. 2007 Apr;84(4):707-17. doi: 10.1016/j.exer.2006.12.014. Epub 2007 Jan 4.
Thrombospondin-4 (TSP-4), a large pentameric glycoprotein of the extracellular matrix, has been described as a neurite outgrowth-promoting molecule. However, the means by which TSP-4 promotes neurite outgrowth in the developing eye is unclear. Here we show that TSP-4 is present at the appropriate time in development and displays a localization pattern within the developing mouse retina consistent with a role in retinal ganglion cell (RGC) neurite outgrowth. Furthermore, results indicate that while TSP-4 alone does not support adhesion or neurite extension, it enhances the ability of laminins to promote adhesion and neurite outgrowth of embryonic retinal cells. The mechanism of enhancement is, in part, based on the ability of TSP-4 to enhance the three-dimensionality and/or clustering of laminins within the substrate matrix. These results support a model where TSP-4 acts as an organizer of adhesive and axon outgrowth-promoting molecules in the ECM to optimize retinal ganglion cell responses.
血小板反应蛋白-4（TSP-4）是细胞外基质中的一种大型五聚体糖蛋白，已被描述为一种促进神经突生长的分子。然而，TSP-4在发育中的眼睛中促进神经突生长的方式尚不清楚。在这里，我们表明TSP-4在发育的适当时间出现，并在发育中的小鼠视网膜内显示出一种定位模式，这与它在视网膜神经节细胞（RGC）神经突生长中的作用一致。此外，结果表明，虽然单独的TSP-4不支持黏附或神经突延伸，但它增强了层粘连蛋白促进胚胎视网膜细胞黏附和神经突生长的能力。增强的机制部分基于TSP-4增强底物基质中层粘连蛋白的三维结构和/或聚集的能力。这些结果支持了一个模型，即TSP-4作为细胞外基质中黏附分子和促进轴突生长分子的组织者，以优化视网膜神经节细胞的反应。
