Expression and alternative splicing of classical and nonclassical MHCI genes in the hippocampus and neuromuscular junction

Abstract

The major histocompatibility complex class I (MHCI) is a large gene family, with over 30 members in mouse. Some MHCIs are well-known for their critical roles in the immune response. Studies in mice which lack stable cell-surface expression of many MHCI proteins suggest that one or more MHCIs also play unexpected, essential roles in the establishment, function, and modification of neuronal synapses in the central nervous system (CNS). However, there is little information about which genes mediate MHCI’s effects in neurons. In this study, RT-PCR was used to simultaneously assess transcription of many MHCI genes in regions of the central and peripheral nervous system where MHCI has a known or suspected role. In the hippocampus, a part of the CNS where MHCI regulates synapse density, synaptic transmission, and plasticity, we found that more than a dozen MHCI genes are transcribed. Single-cell RT-PCR revealed that individual hippocampal neurons can express more than one MHCI gene, and that the MHCI gene expression profile of CA1 pyramidal neurons differs significantly from that of CA3 pyramidal neurons or granule cells of the dentate gyrus. MHCI gene expression was also assessed at the neuromuscular junction (NMJ), a part of the peripheral nervous system (PNS) where MHCI plays a role in neuronal regeneration, and could potentially influence developmental synapse elimination. Four MHCI genes are expressed at the NMJ at an age when synapse elimination is occurring in three different muscles. Several MHCI mRNA splice variants were detected in hippocampus, but not at the NMJ. Together, these results establish the first profile of MHCI gene expression at the developing NMJ, and demonstrate that MHCI gene expression is under tight spatial and temporal regulation in the nervous system. They also identify more than a dozen MHCIs that could play important roles in synaptic transmission and plasticity in the central and peripheral nervous systems.

Neuronal NLRC5 regulates MHC class I expression in Neuro‐2a cells and also during hippocampal development

“…P8 and P15 are two important periods of synaptic development. While synapse elimination is ongoing at P8, synapse elimination has largely concluded by age P15 (Tetruashvily et al ). Thus, the expression timeline of MHC I proteins is tightly correlated with their roles in synaptic remodeling.…”

Immunobiological properties of neurogenic cells of the fetal brain. І. Expression of molecules with immune properties

“…Крім того, експресія МНС І регулюється нейрональною активністю і залучається в гомеостатичну регуляцію функції та морфологічної структури синапсів протягом індивідуального розвитку і у відповідь на блокаду нейрональної активності [68]. Нещодавні дослідження підтвердили роль МНС І у розвитку ЦНС, регуляції росту нейритів і синаптичної пластичності преі постнатального мозку, що розвивається [35,54,55,[69][70][71].…”

Tight Regulation of Major Histocompatibility Complex I for the Spatial and Temporal Expression in the Hippocampal Neurons

“…HLA (human leucocyte antigen) is the MHC antigen specific to humans, and HLA-A, HLA-B and HLA-C are the three types of classical human MHC class I proteins. Mouse MHC antigen is called H-2 antigen, and there are three classical mouse class I proteins: H2-K, H2-D, and H2-L. C57BL/6 mice only express two of them: H2-K b and H2-D b (MHC haplotype b) (Tetruashvily et al, 2016). As of today, the roles of classical MHC I proteins in the establishment, function, and modification of synapses have been extensively reviewed (Boulanger and Shatz, 2004;Boulanger, 2009;Shatz, 2009;Elmer and McAllister, 2012;McAllister, 2014).…”