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.
| Language | English |
|---|---|
| Pages | 735-744 |
| Number of pages | 10 |
| Journal | Journal of Cell Science |
| Volume | 122 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 1 Mar 2009 |
Fingerprint
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
}
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 journal › Article
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 -