Welcher A A, Suter U, De Leon M, Snipes G J, Shooter E M
Department of Neurobiology, Stanford University School of Medicine, CA 94305-5401.
Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7195-9. doi: 10.1073/pnas.88.16.7195.
Striking features of the cellular response to sciatic nerve injury are the proliferation of Schwann cells in the distal nerve stump and the downregulation of myelin-specific gene expression. Once the axons regrow, the Schwann cells differentiate again to reform the myelin sheaths. We have isolated a rat cDNA, SR13, which is strongly downregulated in the initial phase after sciatic nerve injury. This cDNA encodes a glycoprotein that shares striking amino acid similarity with a purified myelin protein and is specifically precipitated by a myelin-specific antiserum. Immunohistochemistry experiments using peptide-specific polyclonal antibodies localize the SR13 protein to the myelin sheath of the sciatic nerve. Computer-aided sequence analysis identified a pronounced homology of SR13 to a growth arrest-specific mRNA (Gas-3) that is expressed in resting but not in proliferating 3T3 mouse fibroblasts. SR13 is similarly downregulated during Schwann cell proliferation in the rat sciatic nerve. The association of the SR13 as well as the Gas-3 mRNA with nonproliferating cells in two different experimental systems suggests a common role for these molecules in maintaining the quiescent cell state.
细胞对坐骨神经损伤反应的显著特征是远端神经残端施万细胞的增殖以及髓鞘特异性基因表达的下调。一旦轴突再生,施万细胞会再次分化以重新形成髓鞘。我们分离出了一个大鼠cDNA,即SR13,它在坐骨神经损伤后的初始阶段被强烈下调。该cDNA编码一种糖蛋白,与一种纯化的髓鞘蛋白具有显著的氨基酸相似性,并被一种髓鞘特异性抗血清特异性沉淀。使用肽特异性多克隆抗体的免疫组织化学实验将SR13蛋白定位到坐骨神经的髓鞘。计算机辅助序列分析确定SR13与生长停滞特异性mRNA(Gas-3)有明显的同源性,Gas-3在静止的3T3小鼠成纤维细胞中表达,但在增殖的细胞中不表达。在大鼠坐骨神经施万细胞增殖过程中,SR13同样被下调。在两个不同的实验系统中,SR13以及Gas-3 mRNA与非增殖细胞的关联表明这些分子在维持细胞静止状态中具有共同作用。