Freidin Mona, Asche Samantha, Bargiello Thaddeus A, Bennett Michael V L, Abrams Charles K
Department of Neurology, State University of New York Downstate at Brooklyn, Brooklyn NY 10021, USA.
Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3567-72. doi: 10.1073/pnas.0813413106. Epub 2009 Feb 13.
Connexin 32 (Cx32), a gap junction protein, is found within the para-nodal region and Schmidt-Lanterman incisures of myelinating Schwann cells (SCs). In developing and regenerating peripheral nerves, pro-myelinating SCs express Cx32 mRNA and protein in conjunction with the expression of myelin specific genes. Neuregulin-1 (Nrg1), a member of the neuregulin family of growth factors, controls SC proliferation and differentiation depending on the cellular environment and the particular stage of SC maturation. Primary cultures of purified SCs from newborn mouse sciatic nerve were used to characterize both the role of Nrg1 in the expression of Cx32 and, conversely, the role of Cx32 in SC responsiveness to Nrg1. Glial growth factor 2, an isoform of Nrg1, up-regulated Cx32 in both proliferating and non-proliferating SCs. However, SCs from Cx32-KO mice exhibited a significantly smaller mitogenic response to glial growth factor 2. Electrical coupling between Cx32-KO SCs did not differ from that between WT SCs, indicating the presence of other connexins. These results suggest a link between Cx32 expression and Nrg1 regulation of SC proliferation that does not involve Cx32-mediated intercellular communication.
连接蛋白32（Cx32）是一种间隙连接蛋白，存在于有髓施万细胞（SCs）的结旁区和施密特-兰特尔曼切迹内。在发育和再生的周围神经中，促髓鞘形成的SCs会同时表达Cx32 mRNA和蛋白以及髓鞘特异性基因。神经调节蛋白-1（Nrg1）是神经调节蛋白家族生长因子的成员之一，它根据细胞环境和SCs成熟的特定阶段来控制SCs的增殖和分化。从小鼠新生坐骨神经中纯化得到的SCs原代培养物被用于研究Nrg1在Cx32表达中的作用，反之，也用于研究Cx32在SCs对Nrg1反应中的作用。神经调节蛋白-1的一种同工型——胶质生长因子2，在增殖和非增殖的SCs中均上调了Cx32的表达。然而，来自Cx32基因敲除（KO）小鼠的SCs对胶质生长因子2的促有丝分裂反应明显较小。Cx32-KO SCs之间的电偶联与野生型（WT）SCs之间的电偶联没有差异，这表明存在其他连接蛋白。这些结果表明Cx32表达与Nrg1对SCs增殖的调节之间存在联系，且这种联系不涉及Cx32介导的细胞间通讯。
