AMPA receptors and their minions: auxiliary proteins in AMPA receptor trafficking

Cell Mol Life Sci. 2019 Jun;76(11):2133-2169. doi: 10.1007/s00018-019-03068-7. Epub 2019 Apr 1.


To correctly transfer information, neuronal networks need to continuously adjust their synaptic strength to extrinsic stimuli. This ability, termed synaptic plasticity, is at the heart of their function and is, thus, tightly regulated. In glutamatergic neurons, synaptic strength is controlled by the number and function of AMPA receptors at the postsynapse, which mediate most of the fast excitatory transmission in the central nervous system. Their trafficking to, at, and from the synapse, is, therefore, a key mechanism underlying synaptic plasticity. Intensive research over the last 20 years has revealed the increasing importance of interacting proteins, which accompany AMPA receptors throughout their lifetime and help to refine the temporal and spatial modulation of their trafficking and function. In this review, we discuss the current knowledge about the roles of key partners in regulating AMPA receptor trafficking and focus especially on the movement between the intracellular, extrasynaptic, and synaptic pools. We examine their involvement not only in basal synaptic function, but also in Hebbian and homeostatic plasticity. Included in our review are well-established AMPA receptor interactants such as GRIP1 and PICK1, the classical auxiliary subunits TARP and CNIH, and the newest additions to AMPA receptor native complexes.

Keywords: AMPA receptors; CNIH; GRIP1; MAGUK; PICK1; Synapse; TARP; Trafficking.

Publication types

  • Review

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Egg Proteins / genetics
  • Egg Proteins / metabolism
  • Gene Expression Regulation
  • Glutamic Acid / metabolism
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Nerve Net / physiology*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neural Networks, Computer
  • Neuronal Plasticity / physiology*
  • Neurons / cytology
  • Neurons / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Transport
  • Receptors, AMPA / genetics
  • Receptors, AMPA / metabolism*
  • Synapses / metabolism
  • Synaptic Transmission


  • CNIH1 protein, human
  • Carrier Proteins
  • Egg Proteins
  • GRIP1 protein, human
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • PICk1 protein, human
  • Receptors, AMPA
  • TARP
  • Glutamic Acid