Integrated Omics Center, Life Health Division, Korea Institute of Science and Technology, Seoul, Korea.
BMB Rep. 2011 Mar;44(3):182-6. doi: 10.5483/BMBRep.2011.44.3.182.
Exogenous stimuli such as nerve growth factor (NGF) exert their effects on neurite outgrowth via Trk neurotrophin receptors. TrkA receptors are known to be ubiquitinated via proteasome inhibition in the presence of NGF. However, the effect of proteasome inhibition on neurite outgrowth has not been studied extensively. To clarify these issues, we investigated signaling events in PC12 cells treated with NGF and the proteasome inhibitor MG132. We found that MG132 facilitated NGF-induced neurite outgrowth and potentiated the phosphorylation of the extracellular signal-regulated kinase/mitogen- activated protein kinase (ERK/MAPK) and phosphatidylinositol- 3-kinase (PI3K)/AKT pathways and TrkA receptors. MG132 stimulated internalization of surface TrkA receptor and stabilized intracellular TrkA receptor, and the Ub(K63) chain was found to be essential for stability. These results indicate that the ubiquitin-proteasome system potentiated neurite formation by regulating the stability of TrkA receptors.
外源性刺激物，如神经生长因子 (NGF)，通过 Trk 神经营养因子受体发挥其对轴突生长的作用。已知 TrkA 受体在 NGF 存在下通过蛋白酶体抑制被泛素化。然而，蛋白酶体抑制对轴突生长的影响尚未得到广泛研究。为了阐明这些问题，我们研究了用 NGF 和蛋白酶体抑制剂 MG132 处理的 PC12 细胞中的信号事件。我们发现 MG132 促进了 NGF 诱导的轴突生长，并增强了细胞外信号调节激酶/丝裂原激活蛋白激酶 (ERK/MAPK) 和磷脂酰肌醇-3-激酶 (PI3K)/AKT 途径和 TrkA 受体的磷酸化。MG132 刺激表面 TrkA 受体的内化并稳定细胞内 TrkA 受体，并且发现 Ub(K63) 链对于稳定性是必需的。这些结果表明，泛素-蛋白酶体系统通过调节 TrkA 受体的稳定性来增强神经突的形成。
