The function of glutamatergic synapses is not perturbed by severe knockdown of 4.1N and 4.1G expression.
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.
Wozny
Christian
C
Neuroscience Research Center, Charité-Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany.
Breustedt
Jörg
J
Wolk
Friederike
F
Varoqueaux
Frédérique
F
Boretius
Susann
S
Zivkovic
Aleksandar R
AR
Neeb
Antje
A
Frahm
Jens
J
Schmitz
Dietmar
D
Brose
Nils
N
Ivanovic
Aleksandra
A
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D018390:Gene Targeting; D018698:Glutamic Acid / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure
D003598:Cytoskeletal Proteins; C540651:Epb4.1l2 protein, mouse; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009479:Neuropeptides; D017470:Receptors, Glutamate; C120557:erythrocyte membrane protein band 4.1-like 1; D018698:Glutamic Acid