Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Mol Psychiatry. 2012 Jan;17(1):1, 99-107. doi: 10.1038/mp.2011.35. Epub 2011 Apr 12.
Neuregulin 1 (NRG1) is a secreted trophic factor that activates the postsynaptic erbB4 receptor tyrosine kinase. Both NRG1 and erbB4 have been repeatedly associated with schizophrenia, but their downstream targets are not well characterized. ErbB4 is highly abundant in interneurons, and NRG1-mediated erbB4 activation has been shown to modulate interneuron function, but the role for NRG1-erbB4 signaling in regulating interneuron dendritic growth is not well understood. Here we show that NRG1/erbB4 promote the growth of dendrites in mature interneurons through kalirin, a major dendritic Rac1-GEF. Recent studies have shown associations of the KALRN gene with schizophrenia. Our data point to an essential role of phosphorylation in kalirin-7's C terminus as the critical site for these effects. As reduced interneuron dendrite length occurs in schizophrenia, understanding how NRG1-erbB4 signaling modulates interneuron dendritic morphogenesis might shed light on disease-related alterations in cortical circuits.
神经调节蛋白 1（NRG1）是一种分泌性营养因子，可激活突触后 erbB4 受体酪氨酸激酶。NRG1 和 erbB4 都与精神分裂症反复相关，但它们的下游靶标尚未很好地表征。erbB4 在中间神经元中含量丰富，并且已经表明 NRG1 介导的 erbB4 激活可调节中间神经元功能，但 NRG1-erbB4 信号在调节中间神经元树突生长中的作用尚不清楚。在这里，我们通过 kalirin（一种主要的树突 Rac1-GEF）显示 NRG1/erbB4 可促进成熟中间神经元的树突生长。最近的研究表明 KALRN 基因与精神分裂症有关。我们的数据表明，kalirin-7 的 C 末端磷酸化在这些效应中是关键位点。由于精神分裂症中中间神经元树突长度减少，因此了解 NRG1-erbB4 信号如何调节中间神经元树突形态发生可能会揭示皮质回路中与疾病相关的改变。
