Gonzalez-Brito Manuel R, Bixby John L
Department of Pediatrics, The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Lois Pope LIFE Center, Room 4-17, 1095 NW 14th Terrace, Miami, FL 33136, USA.
Int J Dev Neurosci. 2006 Nov;24(7):425-9. doi: 10.1016/j.ijdevneu.2006.08.006. Epub 2006 Oct 10.
The full-length extracellular domain (ECD) of protein tyrosine phosphatase delta (PTP-delta) functions as a ligand to promote cell adhesion and neurite outgrowth; this ECD contains three immunoglobulin (Ig) repeats and eight fibronectin type III (FN III) repeats. However, it is not known which regions of the ECD regulate its ligand functions. Therefore, we constructed and expressed a fusion protein of the PTP-delta ECD lacking FN III repeats 4-8, and tested this protein for neuronal adhesion and neurite-promoting ability. Compared to the full-length isoform, the truncated ECD was poorer at promoting adhesion, but a more potent promoter of neurite growth. The results suggest that distal FN III repeats of PTP-delta are important in adhesive functions, but dispensable for neurite outgrowth promotion. As the predominant isoform of PTP-delta during neural development (type D) also lacks distal FN III repeats, the functional properties we observe may be relevant to periods of axon extension, suggesting that splice variants of receptor PTPs play distinct roles in neural development.
蛋白酪氨酸磷酸酶δ（PTP-δ）的全长细胞外结构域（ECD）作为一种配体，可促进细胞黏附和神经突生长；该ECD包含三个免疫球蛋白（Ig）重复序列和八个纤连蛋白III型（FN III）重复序列。然而，尚不清楚ECD的哪些区域调节其配体功能。因此，我们构建并表达了一种缺失FN III重复序列4-8的PTP-δ ECD融合蛋白，并测试了该蛋白的神经元黏附及促神经突生长能力。与全长异构体相比，截短的ECD在促进黏附方面较差，但却是更有效的神经突生长促进剂。结果表明，PTP-δ的远端FN III重复序列在黏附功能中很重要，但对促进神经突生长并非必需。由于神经发育过程中PTP-δ的主要异构体（D型）也缺乏远端FN III重复序列，我们观察到的功能特性可能与轴突延伸期相关，这表明受体型蛋白酪氨酸磷酸酶的剪接变体在神经发育中发挥着不同的作用。
