SUMOylation and phosphorylation of GluK2 regulate kainate receptor trafficking and synaptic plasticity

Sophie E. L. Chamberlain; Maria Inmaculada Gonzalez; Kevin A. Wilkinson; Filip A. Konopacki; S Kantamneni; Jeremy M. Henley; Jack R. Mellor

doi:10.1038/nn.3089

SUMOylation and phosphorylation of GluK2 regulate kainate receptor trafficking and synaptic plasticity

Sophie E. L. Chamberlain, Maria Inmaculada Gonzalez, Kevin A. Wilkinson, Filip A. Konopacki, S Kantamneni, Jeremy M. Henley, Jack R. Mellor^*

^*Corresponding author for this work

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

89 Citations (Scopus)

Abstract

Phosphorylation or SUMOylation of the kainate receptor (KAR) subunit GluK2 have both individually been shown to regulate KAR surface expression. However, it is unknown whether phosphorylation and SUMOylation of GluK2 are important for activity-dependent KAR synaptic plasticity. We found that protein kinase C-mediated phosphorylation of GluK2 at serine 868 promotes GluK2 SUMOylation at lysine 886 and that both of these events are necessary for the internalization of GluK2-containing KARs that occurs during long-term depression of KAR-mediated synaptic transmission at rat hippocampal mossy fiber synapses.

Conversely, phosphorylation of GluK2 at serine 868 in the absence of SUMOylation led to an increase in KAR surface expression by facilitating receptor recycling between endosomal compartments and the plasma membrane. Our results suggest a role for the dynamic control of synaptic SUMOylation in the regulation of KAR synaptic transmission and plasticity.

Original language	English
Pages (from-to)	845-852
Number of pages	8
Journal	Nature Neuroscience
Volume	15
Issue number	6
Early online date	22 Apr 2012
DOIs	https://doi.org/10.1038/nn.3089
Publication status	Published - Jun 2012

Keywords

PROTEIN-KINASE-C
DIFFERENTIAL REGULATION
SURFACE EXPRESSION
CELL BIOLOGY
TRANSMISSION
MEMBRANE
GLUR6
SUMO
AMPA
MECHANISMS

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@article{9259b26738be44489394048024c11414,

title = "SUMOylation and phosphorylation of GluK2 regulate kainate receptor trafficking and synaptic plasticity",

abstract = "Phosphorylation or SUMOylation of the kainate receptor (KAR) subunit GluK2 have both individually been shown to regulate KAR surface expression. However, it is unknown whether phosphorylation and SUMOylation of GluK2 are important for activity-dependent KAR synaptic plasticity. We found that protein kinase C-mediated phosphorylation of GluK2 at serine 868 promotes GluK2 SUMOylation at lysine 886 and that both of these events are necessary for the internalization of GluK2-containing KARs that occurs during long-term depression of KAR-mediated synaptic transmission at rat hippocampal mossy fiber synapses.Conversely, phosphorylation of GluK2 at serine 868 in the absence of SUMOylation led to an increase in KAR surface expression by facilitating receptor recycling between endosomal compartments and the plasma membrane. Our results suggest a role for the dynamic control of synaptic SUMOylation in the regulation of KAR synaptic transmission and plasticity.",

keywords = "PROTEIN-KINASE-C, DIFFERENTIAL REGULATION, SURFACE EXPRESSION, CELL BIOLOGY, TRANSMISSION, MEMBRANE, GLUR6, SUMO, AMPA, MECHANISMS",

author = "Chamberlain, {Sophie E. L.} and Gonzalez, {Maria Inmaculada} and Wilkinson, {Kevin A.} and Konopacki, {Filip A.} and S Kantamneni and Henley, {Jeremy M.} and Mellor, {Jack R.}",

year = "2012",

month = jun,

doi = "10.1038/nn.3089",

language = "English",

volume = "15",

pages = "845--852",

journal = "Nature Neuroscience",

issn = "1097-6256",

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T1 - SUMOylation and phosphorylation of GluK2 regulate kainate receptor trafficking and synaptic plasticity

AU - Chamberlain, Sophie E. L.

AU - Gonzalez, Maria Inmaculada

AU - Wilkinson, Kevin A.

AU - Konopacki, Filip A.

AU - Kantamneni, S

AU - Henley, Jeremy M.

AU - Mellor, Jack R.

PY - 2012/6

Y1 - 2012/6

N2 - Phosphorylation or SUMOylation of the kainate receptor (KAR) subunit GluK2 have both individually been shown to regulate KAR surface expression. However, it is unknown whether phosphorylation and SUMOylation of GluK2 are important for activity-dependent KAR synaptic plasticity. We found that protein kinase C-mediated phosphorylation of GluK2 at serine 868 promotes GluK2 SUMOylation at lysine 886 and that both of these events are necessary for the internalization of GluK2-containing KARs that occurs during long-term depression of KAR-mediated synaptic transmission at rat hippocampal mossy fiber synapses.Conversely, phosphorylation of GluK2 at serine 868 in the absence of SUMOylation led to an increase in KAR surface expression by facilitating receptor recycling between endosomal compartments and the plasma membrane. Our results suggest a role for the dynamic control of synaptic SUMOylation in the regulation of KAR synaptic transmission and plasticity.

AB - Phosphorylation or SUMOylation of the kainate receptor (KAR) subunit GluK2 have both individually been shown to regulate KAR surface expression. However, it is unknown whether phosphorylation and SUMOylation of GluK2 are important for activity-dependent KAR synaptic plasticity. We found that protein kinase C-mediated phosphorylation of GluK2 at serine 868 promotes GluK2 SUMOylation at lysine 886 and that both of these events are necessary for the internalization of GluK2-containing KARs that occurs during long-term depression of KAR-mediated synaptic transmission at rat hippocampal mossy fiber synapses.Conversely, phosphorylation of GluK2 at serine 868 in the absence of SUMOylation led to an increase in KAR surface expression by facilitating receptor recycling between endosomal compartments and the plasma membrane. Our results suggest a role for the dynamic control of synaptic SUMOylation in the regulation of KAR synaptic transmission and plasticity.

KW - PROTEIN-KINASE-C

KW - DIFFERENTIAL REGULATION

KW - SURFACE EXPRESSION

KW - CELL BIOLOGY

KW - TRANSMISSION

KW - MEMBRANE

KW - GLUR6

KW - SUMO

KW - AMPA

KW - MECHANISMS

UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84861570692&partnerID=8YFLogxK

U2 - 10.1038/nn.3089

DO - 10.1038/nn.3089

M3 - Article (Academic Journal)

C2 - 22522402

SN - 1097-6256

VL - 15

SP - 845

EP - 852

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 6

ER -

SUMOylation and phosphorylation of GluK2 regulate kainate receptor trafficking and synaptic plasticity

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MECHANISMS CONTROLLING THE NUMBER AND LOCATION OF SYNAPTIC AMPR'S

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

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SUMOylation and phosphorylation of GluK2 regulate kainate receptor trafficking and synaptic plasticity

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MECHANISMS CONTROLLING THE NUMBER AND LOCATION OF SYNAPTIC AMPR'S

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

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