Regulation of AMPA receptor endocytosis by a signaling mechanism shared with LTD.
The endocytosis of AMPA receptors is thought to be important in the expression of long-term depression (LTD) triggered by NMDA receptor activation. Although signaling pathways necessary for LTD induction have been identified, those responsible for the regulated internalization of AMPA receptors are unknown. Here we show that activation of NMDA receptors alone can trigger AMPA receptor endocytosis through calcium influx and activation of the calcium-dependent protein phosphatase calcineurin. A distinct signaling mechanism mediates the AMPA receptor endocytosis stimulated by insulin. These results demonstrate that although multiple signaling pathways can induce AMPA receptor internalization, NMDA receptor activation enhances AMPA receptor endocytosis via a signaling mechanism required for the induction of LTD.
Beattie
E C
EC
Departments of Psychiatry and Cellular and Molecular Pharmacology, University of California, San Francisco, California 94143, USA.
Carroll
R C
RC
Yu
X
X
Morishita
W
W
Yasuda
H
H
von Zastrow
M
M
Malenka
R C
RC
D000818:Animals; D000831:Animals, Newborn; D019703:Calcineurin / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002451:Cell Compartmentation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D019703:Calcineurin