Zhu X, Lai C, Thomas S, Burden S J
Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA.
EMBO J. 1995 Dec 1;14(23):5842-8. doi: 10.1002/j.1460-2075.1995.tb00272.x.
Neuregulin (NRG) is concentrated at synaptic sites and stimulates expression of acetylcholine receptor (AChR) genes in muscle cells grown in cell culture. These results raise the possibility that NRG is a synaptic signal that activates AChR gene expression in synaptic nuclei. Stimulation of NRG receptors, erbB3 and erbB4 initiates oligomerization between these receptors or between these receptors and other members of the epidermal growth factor (EGF) receptor family, resulting in stimulation of their associated tyrosine kinase activities. To determine which erbBs might mediate synapse-specific gene expression, we used antibodies against each erbB to study their expression in rodent skeletal muscle by immunohistochemistry. We show that erbB2, erbB3 and erbB4 are concentrated at synaptic sites in adult skeletal muscle. ErbB3 and erbB4 remain concentrated at synaptic sites following denervation, indicating that erbB3 and erbB4 are expressed in the postsynaptic membrane. In addition, we show that expression of NRG and erbBs, like AChR gene expression, increases at synaptic sites during postnatal development. The localization of erbB3 and erbB4 at synaptic sites is consistent with the idea that a NRG-stimulated signaling pathway is important for synapse-specific gene expression.
神经调节蛋白（NRG）集中于突触部位，并刺激细胞培养中生长的肌肉细胞中乙酰胆碱受体（AChR）基因的表达。这些结果提示，NRG可能是一种在突触核中激活AChR基因表达的突触信号。刺激NRG受体erbB3和erbB4会引发这些受体之间或这些受体与表皮生长因子（EGF）受体家族其他成员之间的寡聚化，从而刺激其相关的酪氨酸激酶活性。为了确定哪些erbB可能介导突触特异性基因表达，我们使用针对每种erbB的抗体，通过免疫组织化学研究它们在啮齿动物骨骼肌中的表达。我们发现，erbB2、erbB3和erbB4在成年骨骼肌的突触部位集中。去神经支配后，erbB3和erbB4仍集中于突触部位，这表明erbB3和erbB4在突触后膜表达。此外，我们还发现，与AChR基因表达一样，NRG和erbB在出生后发育过程中在突触部位的表达增加。erbB3和erbB4在突触部位的定位与NRG刺激的信号通路对突触特异性基因表达很重要这一观点一致。
