The function of glutamatergic synapses is not perturbed by severe knockdown of 4.1N and 4.1G expression

Christian Wozny, Jörg Breustedt, Friederike Wolk, Frédérique Varoqueaux, Susann Boretius, Aleksandar R. Zivkovic, Antje Neeb, Jens Frahm, Dietmar Schmitz, Nils Brose, Aleksandra Ivanovic

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

AMPA-type glutamate receptors mediate fast excitatory synaptic transmission in the vertebrate brain. Their surface expression at synapses between neurons is regulated in an activity-dependent and activity-independent manner. The protein machinery that regulates synaptic targeting, anchoring and turnover of AMPA receptors consists of several types of specialized scaffolding proteins. The FERM domain scaffolding proteins 4.1G and 4.1N were previously suggested to act jointly in binding and regulating synaptic trafficking of the AMPA receptor subunits GluR1 and GluR4. To determine the functions of 4.1G and 4.1N in vivo, we generated a mutant mouse line that lacks 4.1G entirely and expresses 4.1N at 22% of wild-type levels. These mice had combined 4.1G and 4.1N protein expression in the hippocampus at 12% of wild-type levels (equivalent to 8-10% of combined GluR1 and GluR4 expression levels). They show a moderate reduction in synaptosomal expression levels of the AMPA receptor subunit GluR1 at 3 weeks of age, but no change in basic glutamatergic synaptic transmission and long-term potentiation in the hippocampus. Our study indicates that 4.1G and 4.1N do not have a crucial role in glutamatergic synaptic transmission and the induction and maintenance of long-term plastic changes in synaptic efficacy.

LanguageEnglish
Pages735-744
Number of pages10
JournalJournal of Cell Science
Volume122
Issue number5
DOIs
Publication statusPublished - 1 Mar 2009

Fingerprint

Synaptic Transmission
Synapses
AMPA Receptors
Hippocampus
Long-Term Potentiation
Glutamate Receptors
Vertebrates
Proteins
Neurons
Brain
AMPA 1 glutamate receptor ionotropic
erythrocyte membrane protein band 4.1-like 1
Protein Domains
AMPA 4 glutamate receptor ionotropic

Keywords

  • animals
  • behavior, animal
  • brain
  • cytoskeletal proteins
  • gene targeting
  • glutamic acid
  • membrane proteins
  • mice
  • mice, knockout
  • microfilament proteins
  • neuropeptides
  • patch-clamp techniques
  • receptors, glutamate
  • synapses

Cite this

Wozny, C., Breustedt, J., Wolk, F., Varoqueaux, F., Boretius, S., Zivkovic, A. R., ... Ivanovic, A. (2009). The function of glutamatergic synapses is not perturbed by severe knockdown of 4.1N and 4.1G expression. Journal of Cell Science, 122(5), 735-744. https://doi.org/10.1242/jcs.037382
Wozny, Christian ; Breustedt, Jörg ; Wolk, Friederike ; Varoqueaux, Frédérique ; Boretius, Susann ; Zivkovic, Aleksandar R. ; Neeb, Antje ; Frahm, Jens ; Schmitz, Dietmar ; Brose, Nils ; Ivanovic, Aleksandra. / The function of glutamatergic synapses is not perturbed by severe knockdown of 4.1N and 4.1G expression. In: Journal of Cell Science. 2009 ; Vol. 122, No. 5. pp. 735-744.
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Wozny, C, Breustedt, J, Wolk, F, Varoqueaux, F, Boretius, S, Zivkovic, AR, Neeb, A, Frahm, J, Schmitz, D, Brose, N & Ivanovic, A 2009, 'The function of glutamatergic synapses is not perturbed by severe knockdown of 4.1N and 4.1G expression' Journal of Cell Science, vol. 122, no. 5, pp. 735-744. https://doi.org/10.1242/jcs.037382

The function of glutamatergic synapses is not perturbed by severe knockdown of 4.1N and 4.1G expression. / Wozny, Christian; Breustedt, Jörg; Wolk, Friederike; Varoqueaux, Frédérique; Boretius, Susann; Zivkovic, Aleksandar R.; Neeb, Antje; Frahm, Jens; Schmitz, Dietmar; Brose, Nils; Ivanovic, Aleksandra.

In: Journal of Cell Science, Vol. 122, No. 5, 01.03.2009, p. 735-744.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The function of glutamatergic synapses is not perturbed by severe knockdown of 4.1N and 4.1G expression

AU - Wozny, Christian

AU - Breustedt, Jörg

AU - Wolk, Friederike

AU - Varoqueaux, Frédérique

AU - Boretius, Susann

AU - Zivkovic, Aleksandar R.

AU - Neeb, Antje

AU - Frahm, Jens

AU - Schmitz, Dietmar

AU - Brose, Nils

AU - Ivanovic, Aleksandra

PY - 2009/3/1

Y1 - 2009/3/1

N2 - AMPA-type glutamate receptors mediate fast excitatory synaptic transmission in the vertebrate brain. Their surface expression at synapses between neurons is regulated in an activity-dependent and activity-independent manner. The protein machinery that regulates synaptic targeting, anchoring and turnover of AMPA receptors consists of several types of specialized scaffolding proteins. The FERM domain scaffolding proteins 4.1G and 4.1N were previously suggested to act jointly in binding and regulating synaptic trafficking of the AMPA receptor subunits GluR1 and GluR4. To determine the functions of 4.1G and 4.1N in vivo, we generated a mutant mouse line that lacks 4.1G entirely and expresses 4.1N at 22% of wild-type levels. These mice had combined 4.1G and 4.1N protein expression in the hippocampus at 12% of wild-type levels (equivalent to 8-10% of combined GluR1 and GluR4 expression levels). They show a moderate reduction in synaptosomal expression levels of the AMPA receptor subunit GluR1 at 3 weeks of age, but no change in basic glutamatergic synaptic transmission and long-term potentiation in the hippocampus. Our study indicates that 4.1G and 4.1N do not have a crucial role in glutamatergic synaptic transmission and the induction and maintenance of long-term plastic changes in synaptic efficacy.

AB - AMPA-type glutamate receptors mediate fast excitatory synaptic transmission in the vertebrate brain. Their surface expression at synapses between neurons is regulated in an activity-dependent and activity-independent manner. The protein machinery that regulates synaptic targeting, anchoring and turnover of AMPA receptors consists of several types of specialized scaffolding proteins. The FERM domain scaffolding proteins 4.1G and 4.1N were previously suggested to act jointly in binding and regulating synaptic trafficking of the AMPA receptor subunits GluR1 and GluR4. To determine the functions of 4.1G and 4.1N in vivo, we generated a mutant mouse line that lacks 4.1G entirely and expresses 4.1N at 22% of wild-type levels. These mice had combined 4.1G and 4.1N protein expression in the hippocampus at 12% of wild-type levels (equivalent to 8-10% of combined GluR1 and GluR4 expression levels). They show a moderate reduction in synaptosomal expression levels of the AMPA receptor subunit GluR1 at 3 weeks of age, but no change in basic glutamatergic synaptic transmission and long-term potentiation in the hippocampus. Our study indicates that 4.1G and 4.1N do not have a crucial role in glutamatergic synaptic transmission and the induction and maintenance of long-term plastic changes in synaptic efficacy.

KW - animals

KW - behavior, animal

KW - brain

KW - cytoskeletal proteins

KW - gene targeting

KW - glutamic acid

KW - membrane proteins

KW - mice

KW - mice, knockout

KW - microfilament proteins

KW - neuropeptides

KW - patch-clamp techniques

KW - receptors, glutamate

KW - synapses

U2 - 10.1242/jcs.037382

DO - 10.1242/jcs.037382

M3 - Article

VL - 122

SP - 735

EP - 744

JO - Journal of Cell Science

T2 - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 5

ER -