diffusion barriers constrain receptors at synapses扩散壁垒限制在突触受体.pdfVIP

Diffusion Barriers Constrain Receptors at Synapses ¤a ¤b ´ ¤c Marianne Renner, Claude Schweizer , Hiroko Bannai , Antoine Triller*, Sabine Levi* ´ ´ ´ Institut de Biologie de l’Ecole Normale Superieure (IBENS), Institut National de la Sante et de la Recherche Medicale U1024, Centre National de la Recherche Scientifique UMR8197, Paris, France 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 c- aminobutyric acid type A receptor (GABAAR) 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 ,3- fold 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 GABAAR, the excitatory glutamate receptor 2 subunit (GluA2) of the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic aci