Selective postsynaptic co-localization of MCT2 with AMPA receptor GluR2/3 subunits at excitatory synapses exhibiting AMPA receptor trafficking

Selective postsynaptic co-localization of MCT2 with AMPA receptor GluR2/3 subunits at excitatory synapses exhibiting AMPA receptor trafficking
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DOI:
10.1093/cercor/bhh138
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发表时间:
2005-04-01
期刊:
影响因子:
3.7
通讯作者:
Pellerin, L
Pellerin, L
中科院分区:
医学2区
文献类型:
--
作者:
Bergersen, LH;Magistretti, PJ;Pellerin, L

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MCT2是神经元使用乳酸作为额外能量底物所需的主要神经元单羧酸转运体。先前的证据表明,一些MCT2可能位于谷氨酸突触的突触后元件中。利用包埋后电镜免疫细胞化学证实,MCT2存在于不对称突触的突触后密度、大鼠海马CA1和CA3区辐射层以及小鼠小脑平行纤维-浦肯野细胞突触中。MCT2水平在CA3神经元的苔藓纤维突触中显著降低,而在CA1锥体细胞的对称突触中几乎不存在MCT2。通过定量双标记免疫金细胞化学也可以证明MCT2和AMPA受体GluR2/3亚基在不对称突触中具有相似的突触后分布,并且在突触后密度内具有高水平表达。此外,对于AMPA受体,很大比例的MCT2位于突触后棘的囊泡膜上,形成一个细胞内池,可用于这些兴奋性突触的突触后内/胞外转运。总之,这些数据提供了MCT2在谷氨酸能突触特定亚群突触后密度区表达的证据,也表明MCT2与AMPA受体一样可能经历膜转运。
MCT2 is the main neuronal monocarboxylate transporter needed by neurons if they are to use lactate as an additional energy substrate. Previous evidence suggested that some MCT2 could be located in postsynaptic elements of glutamatergic synapses. Using post-embedding electron microscopic immunocytochemistry, it is demonstrated that MCT2 is present at postsynaptic density of asymmetric synapses, in the stratum radiatum of both rat hippocampal CA1 and CA3 regions, as well as at parallel fibre-Purkinje cell synapses in mouse cerebellum. MCT2 levels were significantly lower at mossy fibre synapses on CA3 neurons, and MCT2 was almost absent from symmetric synapses on CA1 pyramidal cells. It could also be demonstrated using quantitative double-labeling immunogold cytochemistry that MCT2 and AMPA receptor GluR2/3 subunits have a similar postsynaptic distribution at asymmetric synapses with high levels expressed within the postsynaptic density. In addition, as for AMPA receptors, a significant proportion of MCT2 is located on vesicular membranes within the postsynaptic spine, forming an intracellular pool available for a putative postsynaptic endo/exocytotic trafficking at these excitatory synapses. Altogether, the data presented provide evidence for MCT2 expression in the postsynaptic density area at specific subsets of glutamatergic synapses, and also suggest that MCT2, like AMPA receptors, could undergo membrane trafficking.