Neuregulin-1 proteins in rat brain and transfected cells are localized to lipid rafts.
Neuregulin-1 proteins in rat brain and transfected cells are localized to lipid rafts.
复制标题
大鼠脑和转染细胞中的 Neuregulin-1 蛋白定位于脂筏。
DOI：
10.1046/j.1471-4159.2001.t01-1-00132.x
复制
发表时间：
2001
影响因子：
4.7
通讯作者：
Falls,DL
中科院分区：
文献类型：
--
作者：
Frenzel,KE;Falls,DL
NeuRegin-1蛋白及其受体是ErbB受体酪氨酸激酶亚家族的成员，在神经系统和心脏的发育过程中发挥着重要的作用。大多数NeuRegin-1亚型都是以跨膜原蛋白的形式合成的，经过蛋白水解性处理后，产生一个包含有生物活性的EGF样结构域的N-末端片段。在这项研究中，我们调查了是否在脂筏、膜微域中发现了神经调节蛋白，这些微域被认为在信号转导、蛋白质运输和蛋白质降解过程中具有重要作用。我们发现，大鼠脑突触体质膜组分中一个140 kDa的NeuRegin蛋白中有45%不能溶于1%的Triton X-100。浮选梯度分析表明，脑140kDa中性调节蛋白存在于富含 -95的低密度组分中，PSD-95是一种已知的脂筏蛋白。在表达NeuRegin I-β1a或III-β1a亚型的转基因细胞中，大部分NeuRegin前蛋白在1%Triton X-100中不溶，并且在脂筏组分中检测到NeuRegin前蛋白和C末端片段。相反，III-β1a N-末端片段仅在洗涤剂可溶部分中检测到。这些结果表明，神经调节蛋白在脂筏上的定位可能在神经系统内的神经调节蛋白信号传递中发挥作用。
Neuregulin‐1 proteins and their receptors, which are members of the ErbB subfamily of receptor tyrosine kinases, play essential roles in the development of the nervous system and heart. Most neuregulin‐1 isoforms are synthesized as transmembrane proproteins that are proteolytically processed to yield an N‐terminal fragment containing the bioactive EGF‐like domain. In this study we investigated whether neuregulins are found in lipid rafts, membrane microdomains hypothesized to have important roles in signal transduction, protein trafficking, and proteolytic processing. We found that 45% of a 140‐kDa neuregulin protein in rat brain synaptosomal plasma membrane fractions was insoluble in 1% Triton X‐100. Flotation gradient analysis demonstrated the presence of the brain 140 kDa neuregulin protein in low‐density fractions enriched in PSD‐95, a known lipid raft protein. In transfected cells expressing the neuregulin I‐β1a or the III‐β1a isoform, most of the neuregulin proprotein was insoluble in 1% Triton X‐100, and neuregulin proproteins and C‐terminal fragments were detected in lipid raft fractions. In contrast, the III‐β1a N‐terminal fragment was detected only in the detergent‐soluble fraction. These results suggest that localization of neuregulins to lipid rafts may play a role in neuregulin signaling within the nervous system.