Regulation of neuronal functions by the E3-ubiquitinligase Protein Associated with MYC (MYCBP2)

Abstract

The E3-ubiquitinligase MYCBP2 regulates neuronal growth, synaptogenesis, and synaptic plasticity by modulating several signalling 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.

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Figures and Tables

Figure 1 Schematic of the MYCBP2/p38MAPK signaling pathway regulating receptor internalizations. MYCBP2 and its ortholog RPM-1 inhibit the p38 MAPK cascade by targeting MAP3K12 for proteosomal degradation. Activated p38 MAPK prevents the internalization of the TRPV1 at nociceptors of mice, while facilitates at central interneurons of C. elegans the internalization of AMPA receptors.

Table 1 Viability of MYCBP2-knockout animals

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