Arc/Arg3.1 interacts with the endocytic machinery to regulate AMPA receptor trafficking.
Arc/Arg3.1 is an immediate-early gene whose mRNA is rapidly transcribed and targeted to dendrites of neurons as they engage in information processing and storage. Moreover, Arc/Arg3.1 is known to be required for durable forms of synaptic plasticity and learning. Despite these intriguing links to plasticity, Arc/Arg3.1's molecular function remains enigmatic. Here, we demonstrate that Arc/Arg3.1 protein interacts with dynamin and specific isoforms of endophilin to enhance receptor endocytosis. Arc/Arg3.1 selectively modulates trafficking of AMPA-type glutamate receptors (AMPARs) in neurons by accelerating endocytosis and reducing surface expression. The Arc/Arg3.1-endocytosis pathway appears to regulate basal AMPAR levels since Arc/Arg3.1 KO neurons exhibit markedly reduced endocytosis and increased steady-state surface levels. These findings reveal a novel molecular pathway that is regulated by Arc/Arg3.1 and likely contributes to late-phase synaptic plasticity and memory consolidation.
Chowdhury
Shoaib
S
Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Shepherd
Jason D
JD
Okuno
Hiroyuki
H
Lyford
Gregory
G
Petralia
Ronald S
RS
Plath
Niels
N
Kuhl
Dietmar
D
Huganir
Richard L
RL
Worley
Paul F
PF
D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000502:physiology*; D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology; D007150:Immunohistochemistry / Q000379:methods; D047468:Immunoprecipitation / Q000379:methods; D016253:Microscopy, Immunoelectron / Q000379:methods; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D011485:Protein Binding / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism; D014162:Transfection / Q000379:methods; D020798:Two-Hybrid System Techniques
D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; C092069:activity regulated cytoskeletal-associated protein; D000217:Acyltransferases; D034281:Dynamins