Inhibition of N-cadherin and β-catenin function reduces axon-induced Schwann cell proliferation
Inhibition of N-cadherin and β-catenin function reduces axon-induced Schwann cell proliferation
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DOI：
10.1002/jnr.21528
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发表时间：
2008-03-01
影响因子：
4.2
通讯作者：
Wanner, Ina B.
中科院分区：
文献类型：
--
作者：
Gess, Burkhard;Halfter, Hartmut;Wanner, Ina B.
N-cadherin和P-catenin参与肿瘤细胞和神经嵴的细胞粘附和细胞周期。两者都在雪旺细胞发育的关键阶段表达，但对它们在SC谱系中的功能知之甚少。我们研究了这些分子在成年大鼠SC-胚胎背根神经节共培养中的作用，方法是使用低ca2 +条件和特异性阻断抗体干扰N-cadherin功能，并使用小干扰RNA （siRNA）降低SC-神经元共培养和成年大鼠SC单培养中的P-catenin表达。n-钙粘蛋白阻断条件可减少SC-轴突结合，减少轴突诱导的SC增殖。在SC单培养中，p -连环蛋白的减少降低了SC对有丝分裂原β 1-heregulin的增殖反应，而在SC- drg共培养中，β -连环蛋白的减少抑制了轴突接触依赖性SC的增殖。用β 1-heregulin刺激SC培养增加了β -连环蛋白的总蛋白量，细胞核提取物中GSK-3 β和p -连环蛋白的磷酸化。总之，我们的研究结果表明，β -连环蛋白和n-钙粘蛋白在轴突诱导的SC增殖中起着以前未被认识到的作用。(c) 2007 Wiley-Liss, Inc。
N-cadherin and P-catenin are involved in cell adhesion and cell cycle in tumor cells and neural crest. Both are expressed at key stages of Schwann cell (SC) development, but little is known about their function in the SC lineage. We studied the role of these molecules in adult rat derived SC-embryonic dorsal root ganglion cocultures by using low-Ca2+ conditions and specific blocking antibodies to interfere with N-cadherin function and by using small interfering RNA (siRNA) to decrease P-catenin expression in both SC-neuron cocultures and adult rat-derived SC monocultures. N-cadherin blocking conditions decreased SC-axon association and reduced axon-induced SC proliferation. In SC monocultures, P-catenin reduction diminished the proliferative response of SCs to the mitogen beta 1-heregulin, and, in SC-DRG cocultures, beta-catenin reduction inhibited axon-contact-dependent SC proliferation. Stimulation of SC cultures with beta 1-heregulin increased total beta-catenin protein amount, phosphorylation of GSK-3 beta and P-catenin presence in nuclear extracts. In conclusion, our findings suggest a previously unrecognized contribution of beta-catenin and N-cadherin to axon-induced SC proliferation. (c) 2007 Wiley-Liss, Inc.