Arc/Arg3.1 Interacts with the Endocytic Machinery to Regulate AMPA Receptor Trafficking

Shoaib Chowdhury; Jason D. Shepherd; Hiroyuki Okuno; Gregory Lyford; Ronald S. Petralia; Niels Plath; Dietmar Kuhl; Richard L. Huganir; Paul F. Worley

doi:10.1016/j.neuron.2006.08.033

Arc/Arg3.1 Interacts with the Endocytic Machinery to Regulate AMPA Receptor Trafficking

Shoaib Chowdhury, Jason D. Shepherd, Hiroyuki Okuno, Gregory Lyford, Ronald S. Petralia, Niels Plath, Dietmar Kuhl, Richard L. Huganir, Paul F. Worley

School of Medicine

Research output: Contribution to journal › Article › peer-review

524 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	445-459
Number of pages	15
Journal	Neuron
Volume	52
Issue number	3
DOIs	https://doi.org/10.1016/j.neuron.2006.08.033
State	Published - Nov 9 2006

Keywords

MOLNEURO
SIGNALING

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.neuron.2006.08.033

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@article{8fbd0de878904d3082bf8ad688b00de9,

title = "Arc/Arg3.1 Interacts with the Endocytic Machinery to Regulate AMPA Receptor Trafficking",

abstract = "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.",

keywords = "MOLNEURO, SIGNALING",

author = "Shoaib Chowdhury and Shepherd, {Jason D.} and Hiroyuki Okuno and Gregory Lyford and Petralia, {Ronald S.} and Niels Plath and Dietmar Kuhl and Huganir, {Richard L.} and Worley, {Paul F.}",

note = "Funding Information: This work was supported by grants from NIMH (P.F.W.), NIMH Conte Center (R.L.H. and P.F.W.), the Howard Hughes Medical Institute (R.L.H.), and the NIH/NIDCD Intramural Program (R.S.P). H.O. was supported by a fellowship from the Human Frontier Science Program Organization. We would like to thank Oswald Steward for helpful discussions and Jennifer Henderson for preliminary studies of Arc/Arg3.1-endophilin interaction. Thanks to Jing Wu for providing the Arc/Arg3.1 Sindbis virus. We also thank Dr. Ya-Xian Wang for help with the immunogold labeling. Endophilin 1, 2, and Dynamin 2 expression constructs were a generous gift from Dr. De Camilli (Yale University). ",

year = "2006",

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doi = "10.1016/j.neuron.2006.08.033",

language = "English (US)",

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T1 - Arc/Arg3.1 Interacts with the Endocytic Machinery to Regulate AMPA Receptor Trafficking

AU - Chowdhury, Shoaib

AU - Shepherd, Jason D.

AU - Okuno, Hiroyuki

AU - Lyford, Gregory

AU - Petralia, Ronald S.

AU - Plath, Niels

AU - Kuhl, Dietmar

AU - Huganir, Richard L.

AU - Worley, Paul F.

N1 - Funding Information: This work was supported by grants from NIMH (P.F.W.), NIMH Conte Center (R.L.H. and P.F.W.), the Howard Hughes Medical Institute (R.L.H.), and the NIH/NIDCD Intramural Program (R.S.P). H.O. was supported by a fellowship from the Human Frontier Science Program Organization. We would like to thank Oswald Steward for helpful discussions and Jennifer Henderson for preliminary studies of Arc/Arg3.1-endophilin interaction. Thanks to Jing Wu for providing the Arc/Arg3.1 Sindbis virus. We also thank Dr. Ya-Xian Wang for help with the immunogold labeling. Endophilin 1, 2, and Dynamin 2 expression constructs were a generous gift from Dr. De Camilli (Yale University).

PY - 2006/11/9

Y1 - 2006/11/9

N2 - 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.

AB - 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.

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ER -

Arc/Arg3.1 Interacts with the Endocytic Machinery to Regulate AMPA Receptor Trafficking

Abstract

Keywords

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