Neuronal MHC Class I Expression Is Regulated by Activity Driven Calcium Signaling.
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-κB 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.
Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Department of Microbiology and Immunology, Medical School, Southeast University, Nanjing, Jiangsu Province, China.
Dan
D
Lv
Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Department of Microbiology and Immunology, Medical School, Southeast University, Nanjing, Jiangsu Province, China.
Yuqing
Y
Shen
Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Department of Microbiology and Immunology, Medical School, Southeast University, Nanjing, Jiangsu Province, China.
Yaqin
Y
Peng
Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Department of Microbiology and Immunology, Medical School, Southeast University, Nanjing, Jiangsu Province, China.
Jiane
J
Liu
Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Department of Microbiology and Immunology, Medical School, Southeast University, Nanjing, Jiangsu Province, China.
Fengqin
F
Miao
Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Department of Microbiology and Immunology, Medical School, Southeast University, Nanjing, Jiangsu Province, China.
Jianqiong
J
Zhang
D000818:Animals; D020013:Calcium Signaling; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005805:Genes, MHC Class I; D006624:Hippocampus / Q000378:metabolism; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism; D012333:RNA, Messenger; D013569:Synapses / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D050856:Interferon Regulatory Factor-1; D016328:NF-kappa B; D012333:RNA, Messenger; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D007608:Kainic Acid