Neuronal cotransport of glycine receptor and the scaffold protein gephyrin.
The dynamics of postsynaptic receptor scaffold formation and remodeling at inhibitory synapses remain largely unknown. Gephyrin, which is a multimeric scaffold protein, interacts with cytoskeletal elements and stabilizes glycine receptors (GlyRs) and individual subtypes of gamma-aminobutyric acid A receptors at inhibitory postsynaptic sites. We report intracellular mobility of gephyrin transports packets over time. Gephyrin units enter and exit active synapses within several minutes. In addition to previous reports of GlyR-gephyrin interactions at plasma membranes, we show cosedimentation and coimmunoprecipitation of both proteins from vesicular fractions. Moreover, GlyR and gephyrin are cotransported within neuronal dendrites and further coimmunoprecipitate and colocalize with the dynein motor complex. As a result, the blockade of dynein function or dynein-gephyrin interaction, as well as the depolymerization of microtubules, interferes with retrograde gephyrin recruitment. Our data suggest a GlyR-gephyrin-dynein transport complex and support the concept that gephyrin-motor interactions contribute to the dynamic and activity-dependent rearrangement of postsynaptic GlyRs, a process thought to underlie the regulation of synaptic strength.
Maas
Christoph
C
Zentrum für Molekulare Neurobiologie Hamburg, Universität Hamburg, D-20251 Hamburg, Germany.
Tagnaouti
Nadia
N
Loebrich
Sven
S
Behrend
Bardo
B
Lappe-Siefke
Corinna
C
Kneussel
Matthias
M
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007700:Kinetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics; D022101:Microtubule-Organizing Center / Q000378:metabolism; D008954:Models, Biological; D020409:Molecular Motor Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics / Q000502:physiology; D016501:Neurites / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015739:Nocodazole / Q000494:pharmacology; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D011485:Protein Binding; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D018009:Receptors, Glycine / Q000378:metabolism*; D013331:Strychnine / Q000494:pharmacology; D016708:Synaptophysin / Q000032:analysis; D014162:Transfection; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000032:analysis
D002352:Carrier Proteins; D029721:Drosophila Proteins; D000072159:Dynactin Complex; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D020409:Molecular Motor Proteins; D010446:Peptide Fragments; D018009:Receptors, Glycine; D016708:Synaptophysin; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C073441:gephyrin; D011189:Potassium Chloride; D004398:Dyneins; D013331:Strychnine; D015739:Nocodazole; D001640:Bicuculline