Frenzel K E, Falls D L
Department of Biology, Emory University, Atlanta, Georgia, USA.
J Neurochem. 2001 Apr;77(1):1-12. doi: 10.1046/j.1471-4159.2001.t01-1-00132.x.
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-beta 1a or the III-beta 1a 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-beta 1a 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.
神经调节蛋白-1（Neuregulin-1）及其受体属于受体酪氨酸激酶的ErbB亚家族成员，在神经系统和心脏发育中发挥着重要作用。大多数神经调节蛋白-1亚型以跨膜前体蛋白的形式合成，这些前体蛋白经过蛋白水解加工，产生一个包含生物活性表皮生长因子（EGF）样结构域的N端片段。在本研究中，我们调查了神经调节蛋白是否存在于脂筏中，脂筏是一种被认为在信号转导、蛋白质运输和蛋白水解加工中起重要作用的膜微区。我们发现，大鼠脑突触体细胞膜组分中140 kDa神经调节蛋白的45%不溶于1% Triton X-100。浮选梯度分析表明，在富含已知脂筏蛋白PSD-95的低密度组分中存在脑140 kDa神经调节蛋白。在表达神经调节蛋白I-β1a或III-β1a亚型的转染细胞中，大多数神经调节蛋白前体蛋白不溶于1% Triton X-100，并且在脂筏组分中检测到神经调节蛋白前体蛋白和C端片段。相比之下，仅在去污剂可溶组分中检测到III-β1a N端片段。这些结果表明，神经调节蛋白在脂筏中的定位可能在神经系统内的神经调节蛋白信号传导中发挥作用。
