Raabe Timothy D, Deadwyler Gail, Varga Jonathan W, Devries George H
Department of Biological Sciences, St. Mary's University, San Antonio, TX 78228, USA.
Glia. 2004 Jan 15;45(2):197-207. doi: 10.1002/glia.10311.
Neuregulins (NRGs) are growth factors present in neurons and glial cells of the central and peripheral nervous systems and play a role in the survival, proliferation, and differentiation of these cells. We now report the localization of the two major isoforms of NRG (alpha and beta) and their receptors (erbB) in cultured Schwann cells and oligodendrocytes isolated from neonatal rat pups. Immunocytochemistry and Western blots for NRG and erbB receptors in defined subcellular fractions were utilized to assess cellular localization. Less differentiated oligodendrocytes contain both NRG isoforms in the cell bodies but not the processes, while only NRG-1beta was found in the nucleus. In contrast, more differentiated oligodendrocytes contained neither isoform in the nucleus while both isoforms were colocalized in the cytoplasm and cell processes. In Schwann cells, both NRG-1beta and NRG-1alpha were colocalized in the cytoplasm and processes. The Schwann cell nucleus had weak immunoreactivity for both NRG-1 isoforms, although NRG-1beta was predominant. ErbB2 and erbB3 receptors, which transduce the NRG-1 signal in Schwann cells, were found throughout the cytoplasm and in the processes and were also localized in the cell nucleus. The nuclear localization of NRG-1 isoforms and/or erbB receptors in both cell types was confirmed by Western blotting of nuclear and cytoplasmic extracts. Stimulation of Schwann cells with mitotic agents increased NRG-1beta expression in the nucleus and dramatically suppressed NRG-1alpha expression throughout the cell. The functional implications of this differential localization in myelinating cells are discussed.
神经调节蛋白（NRGs）是存在于中枢和外周神经系统的神经元和神经胶质细胞中的生长因子，在这些细胞的存活、增殖和分化中发挥作用。我们现在报告NRG的两种主要异构体（α和β）及其受体（erbB）在从新生大鼠幼崽分离的培养雪旺细胞和少突胶质细胞中的定位。利用免疫细胞化学和针对特定亚细胞组分中NRG和erbB受体的蛋白质免疫印迹来评估细胞定位。分化程度较低的少突胶质细胞在细胞体中含有两种NRG异构体，但突起中没有，而仅在细胞核中发现了NRG-1β。相比之下，分化程度较高的少突胶质细胞在细胞核中两种异构体均不存在，而两种异构体在细胞质和细胞突起中共定位。在雪旺细胞中，NRG-1β和NRG-1α均在细胞质和突起中共定位。雪旺细胞核对两种NRG-1异构体的免疫反应性较弱，尽管NRG-1β占主导。在雪旺细胞中传导NRG-1信号的ErbB2和ErbB3受体在整个细胞质和突起中均有发现，并且也定位于细胞核中。通过对细胞核和细胞质提取物进行蛋白质免疫印迹证实了两种细胞类型中NRG-1异构体和/或erbB受体的核定位。用有丝分裂剂刺激雪旺细胞会增加细胞核中NRG-1β的表达，并显著抑制整个细胞中NRG-1α的表达。讨论了这种在髓鞘形成细胞中的差异定位的功能意义。
