Diffusion Barriers Constrain Receptors at Synapses

Abstract

The flux of neurotransmitter receptors in and out of synapses depends on receptor interaction with scaffolding molecules. However, the crowd of transmembrane proteins and the rich cytoskeletal environment may constitute obstacles to the diffusion of receptors within the synapse. To address this question, we studied the membrane diffusion of the caminobutyric acid type A receptor (GABA A R) subunits clustered (c2) or not (a5) at inhibitory synapses in rat hippocampal dissociated neurons. Relative to the extrasynaptic region, c2 and a5 showed reduced diffusion and increased confinement at both inhibitory and excitatory synapses but they dwelled for a short time at excitatory synapses. In contrast, c2 was ,3fold more confined and dwelled ,3-fold longer in inhibitory synapses than a5, indicating faster synaptic escape of a5. Furthermore, using a gephyrin dominant-negative approach, we showed that the increased residency time of c2 at inhibitory synapses was due to receptor-scaffold interactions. As shown for GABA A R, the excitatory glutamate receptor 2 subunit (GluA2) of the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) had lower mobility in both excitatory and inhibitory synapses but a higher residency time at excitatory synapses. Therefore barriers impose significant diffusion constraints onto receptors at synapses where they accumulate or not. Our data further reveal that the confinement and the dwell time but not the diffusion coefficient report on the synapse specific sorting, trapping and accumulation of receptors.

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BibTeX RIS

BibTeX

@article{renner2026diffusion,
  title = {{Diffusion Barriers Constrain Receptors at Synapses}},
  author = {Marianne Renner and Claude Schweizer and Hiroko Bannai and Antoine Triller and Sabine Lévi},
  journal = {PLoS ONE},
  year = {2026},
  month = oct,
  doi = {10.1371/journal.pone.0043032},
  url = {https://hal.science/hal-05782879v1},
  note = {CC BY 4.0},
}

RIS

TY  - JOUR
TI  - Diffusion Barriers Constrain Receptors at Synapses
AU  - Marianne Renner
AU  - Claude Schweizer
AU  - Hiroko Bannai
AU  - Antoine Triller
AU  - Sabine Lévi
PY  - 2026
DA  - 2026/10/07
JO  - PLoS ONE
DO  - 10.1371/journal.pone.0043032
UR  - https://hal.science/hal-05782879v1
AB  - The flux of neurotransmitter receptors in and out of synapses depends on receptor interaction with scaffolding molecules. However, the crowd of transmembrane proteins and the rich cytoskeletal environment may constitute obstacles to the diffusion of receptors within the synapse. To address this question, we studied the membrane diffusion of the caminobutyric acid type A receptor (GABA A R) subunits clustered (c2) or not (a5) at inhibitory synapses in rat hippocampal dissociated neurons. Relative to the extrasynaptic region, c2 and a5 showed reduced diffusion and increased confinement at both inhibitory and excitatory synapses but they dwelled for a short time at excitatory synapses. In contrast, c2 was ,3fold more confined and dwelled ,3-fold longer in inhibitory synapses than a5, indicating faster synaptic escape of a5. Furthermore, using a gephyrin dominant-negative approach, we showed that the increased residency time of c2 at inhibitory synapses was due to receptor-scaffold interactions. As shown for GABA A R, the excitatory glutamate receptor 2 subunit (GluA2) of the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) had lower mobility in both excitatory and inhibitory synapses but a higher residency time at excitatory synapses. Therefore barriers impose significant diffusion constraints onto receptors at synapses where they accumulate or not. Our data further reveal that the confinement and the dwell time but not the diffusion coefficient report on the synapse specific sorting, trapping and accumulation of receptors.
SN  - 1932-6203
SN  - 1932-6203
ER  -

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