Surface trafficking of NMDA receptors: Gathering from a partner to another

Laurent Ladépêche, Julien Pierre Dupuis, Laurent Groc
Seminars in Cell & Developmental Biology. 2014-03-01; 27: 3-13
DOI: 10.1016/j.semcdb.2013.10.005

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Understanding the molecular and cellular pathways by which neurons integrate
signals from different neurotransmitter systems has been among the major
challenges of modern neuroscience. The ionotropic glutamate NMDA receptor plays a
key role in the maturation and plasticity of glutamate synapses, both in
physiology and pathology. It recently appeared that the surface distribution of
NMDA receptors is dynamically regulated through lateral diffusion, providing for
instance a powerful way to rapidly affect the content and composition of synaptic
receptors. The ability of various neuromodulators to regulate NMDA receptor
signaling revealed that this receptor can also serve as a molecular integrator of
the ambient neuronal environment. Although still in its infancy, we here review
our current understanding of the cellular regulation of NMDA receptor surface
dynamics. We specifically discuss the roles of well-known modulators, such as
dopamine, and membrane interactors in these regulatory processes, exemplifying
the recent evidence that the direct interaction between NMDAR and dopamine
receptors regulates their surface diffusion and distribution. In addition to the
well-established modulation of NMDA receptor signaling by intracellular pathways,
the surface dynamics of the receptor is now emerging as the first level of
regulation, opening new pathophysiological perspectives for innovative
therapeutical strategies.

Copyright © 2013. Published by Elsevier Ltd.

Auteurs Bordeaux Neurocampus