期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 278, 期 44, 页码 43525-43532出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M306206200
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资金
- Medical Research Council [G9629038, G9629038(61600)] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
- Medical Research Council [G9629038] Funding Source: researchfish
- MRC [G9629038] Funding Source: UKRI
Little is known about the dynamics of the dendritic transport of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) to synapses. Here, using virally expressed green fluorescent protein (GFP)GluR1 and GFP-GluR2 and confocal photobleach techniques we show near real-time movement of these subunits in living cultured hippocampal neurons. GFP-GluR1 fluorescence was widely distributed throughout the extranuclear compartment with no evidence for discrete intracellular stores. GFP-GluR1 transport was predominantly proximal to distal at rates of 0.2 - 0.4 mum.s(-1). GFP-GluR2 fluorescence was more punctate and localized at or close to the plasma membrane. Overall, GFP-GluR2 movement was less dynamic with distinct mobile and immobile pools. Neither activation nor inhibition of surface-expressed N-methyl-D-aspartate receptors or AMPARs had any significant effect on the rates of GFP-GluR1 or GFP-GluR2 dendritic transport. These results demonstrate that GluR1 is constitutively and rapidly transported throughout the neuron. GluR2, on the other hand, is less mobile, with a majority retained in relatively immobile membrane-associated clusters, with similar to 40% showing synaptic co-localization. Furthermore, the transport of both subunits is activity-independent, suggesting that the regulated delivery of AMPARs to the vicinity of synapses is not a mechanism that is involved in processes such as synaptic plasticity.
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