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Coupling of agonist‐induced AMPA receptor internalization with receptor recycling
Author(s) -
Liang Feng,
Huganir Richard L.
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00377.x
Subject(s) - ampa receptor , internalization , agonist , receptor , microbiology and biotechnology , chemistry , long term depression , biology , glutamate receptor , biochemistry
Excitatory post‐synaptic currents in the CNS are primarily mediated by α‐amino‐3‐hydroxy‐5‐methyl‐isoxazole‐4‐propionic acid (AMPA) receptors in response to glutamate. Internalization of cell‐surface receptors has been shown to be one mechanism by which to control receptor function. To test for agonist control of AMPA receptor plasma membrane expression we used biochemical assays to study AMPA receptor internalization and insertion processes. In heterologous cells, we observed a slow constitutive internalization and a rapid agonist‐induced internalization of AMPA receptors. To our surprise, however, agonist treatment had no effect on the steady‐state levels of AMPA receptors on the cell surface. To examine whether this could be explained by an agonist‐induced increase in the insertion rate of AMPA receptors into the plasma membrane we developed an assay to independently measure receptor insertion. Remarkably, agonist treatment of cells also dramatically increased AMPA receptor plasma membrane insertion rates. In addition, using an assay to measure recycling of internalized pools we found that internalized receptors are rapidly recycled to the cell surface. These results suggest that agonist‐induced receptor internalization is coupled to increases in receptor recycling. This increase in receptor flux through intracellular pools may allow for rapid changes in receptor surface expression by independent regulatory control of internalization and insertion.