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 γ-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.
Neuronal cotransport of glycine receptor and the scaffold protein gephyrin
C. Maas and N. Tagnaouti contributed equally to this paper.
Abbreviations used in this paper: AMPA, α-amino-3-hydroxy-5-methyl- 4-isoxazolepropionate; DHC, dynein heavy chain; DIC, dynein intermediate chain; DLC, dynein light chain; GABAAR, γ-aminobutyric acid A receptor; GlyR, glycine receptor; GRIP1, glutamate receptor–interacting protein 1; HEK, human embryonic kidney; mRFP, monomeric red fluorescent protein; MTOC, microtubule-organizing center; NMDA, N-methyl-d-asparate; VIAAT, vesicular inhibitory amino acid transporter.
Christoph Maas, Nadia Tagnaouti, Sven Loebrich, Bardo Behrend, Corinna Lappe-Siefke, Matthias Kneussel; Neuronal cotransport of glycine receptor and the scaffold protein gephyrin . J Cell Biol 30 January 2006; 172 (3): 441–451. doi: https://doi.org/10.1083/jcb.200506066
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