Dendritic and Axonal Targeting of Type 5 Metabotropic Glutamate Receptor Is Regulated by Homer1 Proteins and Neuronal Excitation
Dendritic and Axonal Targeting of Type 5 Metabotropic Glutamate Receptor Is Regulated by Homer1 Proteins and Neuronal Excitation
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DOI：
10.1523/jneurosci.20-23-08710.2000
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发表时间：
2000-12
期刊：
影响因子：
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通讯作者：
F. Ango;J. Pin;J. Tu;B. Xiao;P. Worley;J. Bockaert;L. Fagni
中科院分区：
文献类型：
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作者：
F. Ango;J. Pin;J. Tu;B. Xiao;P. Worley;J. Bockaert;L. Fagni
神经递质受体的生理作用与其适当的神经室定位密切相关。在这里，我们研究了代谢性谷氨酸受体(MGluR)相互作用蛋白Hmer 1a、b和c在mGluR5靶向神经元中的作用。我们发现mGluR5单独转染培养的小脑颗粒细胞时仅定位于细胞体。相反，当mGluR5与Hmer 1b或Hmer 1c共表达时，mGluR5也在树突中被发现，当与Hmer 1a共转染时，mGluR5在树突和轴突中都被发现。在树突中，共转染的mGluR5和Hmer 1b/c形成了与突触标记突触共同定位的簇。有趣的是，当单独转基因时，荷马蛋白也被转移到轴突，但没有形成这样的簇。用离子型谷氨酸受体激动剂NMDA和海人酸或钾通道阻滞剂四乙基铵和4-氨基吡啶的混合物去极化，即使在Hmer 1a降解很长一段时间后，也能诱导内源性Hmer 1a的瞬时表达和转基因mGluR5的持续神经元定位。这些结果表明，Hmer 1a/b/c蛋白参与了mGluR5靶向树突突触和/或轴突的作用，并且这种作用可以由神经元活动来调节。由于内源性Hmer 1a的活性依赖效应也是持久的，该蛋白对mGluR5的轴突靶向可能在突触可塑性中发挥重要作用。
The physiological actions of neurotransmitter receptors are intimately linked to their proper neuronal compartment localization. Here we studied the effect of the metabotropic glutamate receptor (mGluR)-interacting proteins, Homer1a, b, and c, in the targeting of mGluR5 in neurons. We found that mGluR5 was exclusively localized in cell bodies when transfected alone in cultured cerebellar granule cells. In contrast, mGluR5 was found also in dendrites when coexpressed with Homer1b or Homer1c, and in both dendrites and axons when cotransfected with Homer1a. In dendrites, cotransfected mGluR5 and Homer1b/c formed clusters that colocalized with the synaptic marker synaptophysin. Interestingly when transfected alone, the Homer proteins were also translocated to neurites but did not form such clusters. Depolarization of the neurons with a mixture of ionotropic glutamate receptor agonists, NMDA and kainate, or potassium channel blockers, tetraethylammonium and 4-aminopyridine, induced transient expression of endogenous Homer1a and persistent neuritic localization of transfected mGluR5 even long after degradation of Homer1a. These results suggest that Homer1a/b/c proteins are involved in the targeting of mGluR5 to dendritic synaptic sites and/or axons and that this effect can be regulated by neuronal activity. Because the activity-dependent effect of endogenous Homer1a was also long-lasting, the axonal targeting of mGluR5 by this protein is likely to play an important role in synaptic plasticity.