0000000000761179
AUTHOR
Eric Jacobi
Diversity in AMPA receptor complexes in the brain.
AMPA receptor (AMPAR) complexes comprise four of the AMPAR subunits GluA1-4 and several additional interacting proteins. Subunit composition determines AMPAR function. However, AMPAR function depends to a large extent also on interacting proteins, which influence trafficking to the cell surface, activity-dependent subcellular localization and gating of AMPARs. In this review we report about recent findings on the diversity of AMPAR complexes that allow us to better understand functional properties of native receptors in the brain.
AMPA receptor complex constituents: Control of receptor assembly, membrane trafficking and subcellular localization
Fast excitatory transmission at synapses of the central nervous system is mainly mediated by AMPA receptors (AMPARs). Synaptic AMPAR number and function correlates with synaptic strength. AMPARs are thus key proteins of activity-dependent plasticity in neuronal communication. Up- or down-regulation of synaptic AMPAR number is a tightly controlled dynamic process that involves export of receptors from the endoplasmic reticulum (ER) and Golgi apparatus, exocytosis and endocytosis as well as lateral diffusion of the receptors in the cell membrane. The four AMPAR subunits are embedded into a dynamic network of more than 30 interacting proteins. Many of these proteins are known to modulate recep…
Modulation of information processing by AMPA receptor auxiliary subunits
AMPA-type glutamate receptors (AMPARs) are key molecules of neuronal communication in our brain. The discovery of AMPAR auxiliary subunits, such as proteins of the TARP, CKAMP and CNIH families, fundamentally changed our understanding of how AMPAR function is regulated. Auxiliary subunits control almost all aspects of AMPAR function in the brain. They influence AMPAR assembly, composition, structure, trafficking, subcellular localization and gating. This influence has important implications for synapse function. In the present review, we first discuss how auxiliary subunits affect the strength of synapses by modulating number and localization of AMPARs in synapses as well as their glutamate…
Amyloid Beta-Mediated Changes in Synaptic Function and Spine Number of Neocortical Neurons Depend on NMDA Receptors
Onset and progression of Alzheimer’s disease (AD) pathophysiology differs between brain regions. The neocortex, for example, is a brain region that is affected very early during AD. NMDA receptors (NMDARs) are involved in mediating amyloid beta (Aβ) toxicity. NMDAR expression, on the other hand, can be affected by Aβ. We tested whether the high vulnerability of neocortical neurons for Aβ-toxicity may result from specific NMDAR expression profiles or from a particular regulation of NMDAR expression by Aβ. Electrophysiological analyses suggested that pyramidal cells of 6-months-old wildtype mice express mostly GluN1/GluN2A NMDARs. While synaptic NMDAR-mediated currents are unaltered in 5xFAD …