Assembly, Secretory Pathway Trafficking, and Surface Delivery of Kainate Receptors Is Regulated by Neuronal Activity

Ashley J. Evans; Sonam Gurung; Kevin A. Wilkinson; David J. Stephens; Jeremy M. Henley

doi:10.1016/j.celrep.2017.06.001

Assembly, Secretory Pathway Trafficking, and Surface Delivery of Kainate Receptors Is Regulated by Neuronal Activity

Ashley J. Evans, Sonam Gurung, Kevin A. Wilkinson, David J. Stephens, Jeremy M. Henley

Research output: Contribution to journal › Article (Academic Journal)

16 Citations (Scopus)

305 Downloads (Pure)

Abstract

Summary Ionotropic glutamate receptor (iGluR) trafficking and function underpin excitatory synaptic transmission and plasticity and shape neuronal networks. It is well established that the transcription, translation, and endocytosis/recycling of iGluRs are all regulated by neuronal activity, but much less is known about the activity dependence of iGluR transport through the secretory pathway. Here, we use the kainate receptor subunit GluK2 as a model iGluR cargo to show that the assembly, early secretory pathway trafficking, and surface delivery of iGluRs are all controlled by neuronal activity. We show that the delivery of de novo kainate receptors is differentially regulated by modulation of GluK2 Q/R editing, PKC phosphorylation, and PDZ ligand interactions. These findings reveal that, in addition to short-term regulation of iGluRs by recycling/endocytosis and long-term modulation by altered transcription/translation, the trafficking of iGluRs through the secretory pathway is under tight activity-dependent control to determine the numbers and properties of surface-expressed iGluRs.

Original language	English
Pages (from-to)	2613-2626
Number of pages	14
Journal	Cell Reports
Volume	19
Issue number	12
Early online date	20 Jun 2017
DOIs	https://doi.org/10.1016/j.celrep.2017.06.001
Publication status	Published - 20 Jun 2017

Keywords

kainate receptor
retention using selective hooks
RUSH
secretory pathway
ER exit sites
Golgi outposts
AMPA receptors
scaling
Q/R editing
ADAR2
PDZ ligand

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10.1016/j.celrep.2017.06.001

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Projects

4 Finished

Targets and mechanisms of SUMOylation-mediated cardioprotection during ischemia and reperfusion injury

Henley, J. M.

1/04/15 → 3/10/19

Project: Research

Roles of protein SUMOylation in AMPA receptor trafficking, synaptic dysfunction and cognitive impairment in dementia

Henley, J. M.

1/03/14 → 30/06/18

Project: Research

PROTEIN INTERACTIONS AND POST TRANSATIONAL MODIFICATION IN THE TRAFFICKING OF NEURONAL KAINATE RECEPTORS

Henley, J. M.

1/01/08 → 1/10/11

Project: Research

Equipment

Wolfson Bioimaging Facility

Mark Jepson (Manager)

Faculty of Life Sciences

Facility/equipment: Facility

Profiles

Professor Jeremy M Henley

J.M.Henley@bristol.ac.uk

Fundamental Bioscience
School of Biochemistry - Professor of Molecular Neuroscience
Dynamic Cell Biology
Bristol Neuroscience

Person: Academic , Member

Professor David J Stephens

David.Stephens@bristol.ac.uk

Fundamental Bioscience
School of Biochemistry - Professor of Cell Biology
Dynamic Cell Biology

Person: Academic , Member

Cite this

Evans, A. J., Gurung, S., Wilkinson, K. A., Stephens, D. J., & Henley, J. M. (2017). Assembly, Secretory Pathway Trafficking, and Surface Delivery of Kainate Receptors Is Regulated by Neuronal Activity. Cell Reports, 19(12), 2613-2626. https://doi.org/10.1016/j.celrep.2017.06.001

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abstract = "Summary Ionotropic glutamate receptor (iGluR) trafficking and function underpin excitatory synaptic transmission and plasticity and shape neuronal networks. It is well established that the transcription, translation, and endocytosis/recycling of iGluRs are all regulated by neuronal activity, but much less is known about the activity dependence of iGluR transport through the secretory pathway. Here, we use the kainate receptor subunit GluK2 as a model iGluR cargo to show that the assembly, early secretory pathway trafficking, and surface delivery of iGluRs are all controlled by neuronal activity. We show that the delivery of de novo kainate receptors is differentially regulated by modulation of GluK2 Q/R editing, PKC phosphorylation, and PDZ ligand interactions. These findings reveal that, in addition to short-term regulation of iGluRs by recycling/endocytosis and long-term modulation by altered transcription/translation, the trafficking of iGluRs through the secretory pathway is under tight activity-dependent control to determine the numbers and properties of surface-expressed iGluRs.",

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AU - Evans, Ashley J.

AU - Gurung, Sonam

AU - Wilkinson, Kevin A.

AU - Stephens, David J.

AU - Henley, Jeremy M.

PY - 2017/6/20

Y1 - 2017/6/20

N2 - Summary Ionotropic glutamate receptor (iGluR) trafficking and function underpin excitatory synaptic transmission and plasticity and shape neuronal networks. It is well established that the transcription, translation, and endocytosis/recycling of iGluRs are all regulated by neuronal activity, but much less is known about the activity dependence of iGluR transport through the secretory pathway. Here, we use the kainate receptor subunit GluK2 as a model iGluR cargo to show that the assembly, early secretory pathway trafficking, and surface delivery of iGluRs are all controlled by neuronal activity. We show that the delivery of de novo kainate receptors is differentially regulated by modulation of GluK2 Q/R editing, PKC phosphorylation, and PDZ ligand interactions. These findings reveal that, in addition to short-term regulation of iGluRs by recycling/endocytosis and long-term modulation by altered transcription/translation, the trafficking of iGluRs through the secretory pathway is under tight activity-dependent control to determine the numbers and properties of surface-expressed iGluRs.

AB - Summary Ionotropic glutamate receptor (iGluR) trafficking and function underpin excitatory synaptic transmission and plasticity and shape neuronal networks. It is well established that the transcription, translation, and endocytosis/recycling of iGluRs are all regulated by neuronal activity, but much less is known about the activity dependence of iGluR transport through the secretory pathway. Here, we use the kainate receptor subunit GluK2 as a model iGluR cargo to show that the assembly, early secretory pathway trafficking, and surface delivery of iGluRs are all controlled by neuronal activity. We show that the delivery of de novo kainate receptors is differentially regulated by modulation of GluK2 Q/R editing, PKC phosphorylation, and PDZ ligand interactions. These findings reveal that, in addition to short-term regulation of iGluRs by recycling/endocytosis and long-term modulation by altered transcription/translation, the trafficking of iGluRs through the secretory pathway is under tight activity-dependent control to determine the numbers and properties of surface-expressed iGluRs.

KW - kainate receptor

KW - retention using selective hooks

KW - RUSH

KW - secretory pathway

KW - ER exit sites

KW - Golgi outposts

KW - AMPA receptors

KW - scaling

KW - Q/R editing

KW - ADAR2

KW - PDZ ligand

U2 - 10.1016/j.celrep.2017.06.001

DO - 10.1016/j.celrep.2017.06.001

M3 - Article (Academic Journal)

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SP - 2613

EP - 2626

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

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ER -