Neuronal MHC Class I Expression Is Regulated by Activity Driven Calcium Signaling

作者：Lv, Dan; Shen, Yuqing; Peng, Yaqin; Liu, Jiane; Miao, Fengqin; Zhang, Jianqiong^*

来源：PLos One, 2015, 10(8): e0135223.

DOI：10.1371/journal.pone.0135223

• MAJOR HISTOCOMPATIBILITY COMPLEX
• TRANSCRIPTIONAL REGULATION
• GENE-EXPRESSION
• MOLECULES
• CNS
• FAMILIES
• NLRC5
• RNA

MHC class I (MHC-I) molecules are important components of the immune system. Recently MHC-I have been reported to also play important roles in brain development and synaptic plasticity. In this study, we examine the molecular mechanism(s) underlying activity-dependent MHC-I expression using hippocampal neurons. Here we report that neuronal expression level of MHC-I is dynamically regulated during hippocampal development after birth in vivo. Kainic acid (KA) treatment significantly increases the expression of MHC-I in cultured hippocampal neurons in vitro, suggesting that MHC-I expression is regulated by neuronal activity. In addition, KA stimulation decreased the expression of pre- and post-synaptic proteins. This down-regulation is prevented by addition of an MHC-I antibody to KA treated neurons. Further studies demonstrate that calcium-dependent protein kinase C (PKC) is important in relaying KA simulation activation signals to up-regulated MHC-I expression. This signaling cascade relies on activation of the MAPK pathway, which leads to increased phosphorylation of CREB and NF-kappa B p65 while also enhancing the expression of IRF-1. Together, these results suggest that expression of MHC-I in hippocampal neurons is driven by Ca2+ regulated activation of the MAPK signaling transduction cascade.

• 出版日期2015-8-11
• 单位东南大学