Activity-dependent regulation of dendritic synthesis and trafficking of AMPA receptors.
Regulation of AMPA receptor (AMPAR) trafficking is important for neural plasticity. Here we examined the trafficking and synthesis of the GluR1 and GluR2 subunits using ReAsH-EDT(2) and FlAsH-EDT(2) staining. Activity blockade of rat cultured neurons increased dendritic GluR1, but not GluR2, levels. Examination of transected dendrites revealed that both AMPAR subunits were synthesized in dendrites and that activity blockade enhanced dendritic synthesis of GluR1 but not GluR2. In contrast, acute pharmacological manipulations increased dendritic synthesis of both subunits. AMPARs synthesized in dendrites were inserted into synaptic plasma membranes and, after activity blockade, the electrophysiological properties of native synaptic AMPARs changed in the manner predicted by the imaging experiments. In addition to providing a novel mechanism for synaptic modifications, these results point out the advantages of using FlAsH-EDT(2) and ReAsH-EDT(2) for studying the trafficking of newly synthesized proteins in local cellular compartments such as dendrites.
Ju
William
W
Nancy Friend Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, 1201 Welch Road, Stanford University School of Medicine, Palo Alto, California 94304, USA.
Morishita
Wade
W
Tsui
Jennifer
J
Gaietta
Guido
G
Deerinck
Thomas J
TJ
Adams
Stephen R
SR
Garner
Craig C
CC
Tsien
Roger Y
RY
Ellisman
Mark H
MH
Malenka
Robert C
RC
D000200:Action Potentials / Q000187:drug effects / Q000235:genetics*; D020816:Amino Acid Motifs / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001152:Arsenicals; D002478:Cells, Cultured; D003545:Cysteine; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005333:Fetus; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics*; D010078:Oxazines; D010446:Peptide Fragments; D021381:Protein Transport / Q000502:physiology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics*; D015854:Up-Regulation / Q000502:physiology
D001152:Arsenicals; D003545:Cysteine; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D010078:Oxazines; D010446:Peptide Fragments; D012333:RNA, Messenger; D018091:Receptors, AMPA; C454115:ReAsH-EDT2 compound; C104722:glutamate receptor ionotropic, AMPA 2