MHC class I: an unexpected role in neuronal plasticity

Abstract

For the nervous system to translate experience into memory and behavior, lasting structural change at synapses must occur. This requirement is clearly evident during critical periods of activity-dependent neural development, and accumulating evidence has established a surprising role for the major histocompatibility complex class I (MHCI) proteins in this process.

FIGURE 1

Working model (A) for how MHCI might interact with PirB at or near synapses to regulate plasticity. It is proposed that MHCI is located postsynaptically near glutamate receptors (GLUR’s) based on immunostaining of hippocampal neuron dendrites and colocalization with PSD-95 shown in B. The expression of PirB in axonal growth cones of cortical neurons in vitro (C) suggests a presynaptic location. The iintracellular domain of PirB carries 4 motifs whose phosphorylation (green circles) activates signaling that opposes MAP Kinase and integrin cascades. In this model, PirB would signal when bound to MHCI located across the synapse. Since neural activity regulates MHCI expression levels, PirB could also regulate downstream signaling cascades in an activity-dependent way. (B: modified from Goddard et al, 2007. C: modified from Syken et al, 2006.)