Holland Sabrina, Scholich Klaus
Pharmazentrum frankfurt/ZAFES; Institute of Clinical Pharmacology; Klinikum der Goethe-Universität Frankfurt, Germany.
Commun Integr Biol. 2011 Sep;4(5):513-5. doi: 10.4161/cib.15967. Epub 2011 Sep 1.
The E3-ubiquitinligase MYCBP2 regulates neuronal growth, synaptogenesis and synaptic plasticity by modulating several signaling pathways including the p38 MAPK signaling cascade. We found that loss of MYCBP2 in peripheral sensory neurons inhibits the internalization of transient receptor potential vanilloid receptor 1 (TRPV1) in a p38 MAPK-dependent manner. This prevented desensitization of activity-induced calcium increases and prolongs formalin-induced thermal hyperalgesia in mice. Besides its function in pain perception TRPV1 is also involved in the regulation of neuronal growth. Therefore, the observed effect of MYCBP2 on TRPV1 internalization could be part of the mechanisms underlying its well documented regulatory role in neuronal growth. The clarification of the mechanism is important for the understanding of the different MYCBP2-functions in diverse neuronal subpopulations and species.
E3泛素连接酶MYCBP2通过调节包括p38丝裂原活化蛋白激酶（MAPK）信号级联在内的多种信号通路，调控神经元生长、突触发生和突触可塑性。我们发现，外周感觉神经元中MYCBP2的缺失以p38 MAPK依赖的方式抑制瞬时受体电位香草酸受体1（TRPV1）的内化。这阻止了活性诱导的钙增加的脱敏，并延长了小鼠福尔马林诱导的热痛觉过敏。除了在疼痛感知中的作用外，TRPV1还参与神经元生长的调节。因此，观察到的MYCBP2对TRPV1内化的影响可能是其在神经元生长中充分记录的调节作用的潜在机制的一部分。阐明该机制对于理解MYCBP2在不同神经元亚群和物种中的不同功能很重要。
