Cytoplasmic Signalling by Major Histocompatibility Class-I Proteins Modulates Synaptic Glutamate Receptors

AMPA-type glutamate receptors (AMPARs) and major histocompatibility complex class I (MHC-I) proteins regulate synaptic signalling. Here we describe the importance of the cytoplasmic tail of MHC-I for its role in the central nervous system (CNS) in synaptic signalling and the modulation of synaptic glutamate receptor expression. We demonstrate that Y321F mutation of the conserved cytoplasmic tyrosine in MHC-I affects expression of the AMPAR, GluA2/3, and alters phosphorylation of a number of kinases, including Fyn, Lyn, p38, ERK1/2, JNK1/2/3, and p70 S6 kinase. These data elucidate the important role of MHC-1 on AMPAR function and modifications to the cytoplasmic tail of MHC-1 can alter synaptic strength, plasticity and learning and memory.