AMPA受体是人类神经细胞连接之间的重要调控因子。但荷兰研究人员Helmut Kessels发现,AMPA受体功能的发挥与细胞内AMPA受体的数量无关,而与该受体在细胞膜上的位置有关。因此,仅仅增加细胞内的AMPA受体的数量并不足以调节神经细胞之间的连接。神经细胞之间的连接能够影响我们的学习能力。
这项研究发表在9月版的Nature Neuroscience杂志上。
AMPA受体影响突触可塑性(synaptic plasticity)——即两个神经细胞连接(突触)的强度改变的能力。之前有研究认为,细胞内AMPA受体的数量能够引起神经细胞的连接,从而影响我们的学习能力。
虽然细胞内能够产生大量的AMPA受体,但大部分都被溶酶体所降解。Kessels对AMPA受体两个亚基——GluR1 和GluR2进行研究,这两个亚基对我们学习能力有不同的影响。GluR1对新记忆的形成至关重要,GluR2在记忆储存上具有重要作用。
研究人员通过增加与GluR1相同数量的受体相互作用蛋白stargazin来阻止溶酶体降解GluR1,磷酸化GluR1也能获得同样的效果。然而研究人员发现,细胞内GluR1数量的增加并未增加细胞内受体的数量,也未增加突触的数量。对GluR2的研究也产生了相同的结果。该结论还需要进一步证实是否受体的位置的确可以影响突触可塑性以及我们学习的能力。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature Neuroscience 12, 888 - 896 (2009) 21 June 2009
Roles of stargazin and phosphorylation in the control of AMPA receptor subcellular distribution
Helmut W Kessels1,2, Charles D Kopec1,2, Matthew E Klein1,2 & Roberto Malinow1,2
Abstract
Understanding how the subcellular fate of newly synthesized AMPA receptors (AMPARs) is controlled is important for elucidating the mechanisms of neuronal function. We examined the effect of increased synthesis of AMPAR subunits on their subcellular distribution in rat hippocampal neurons. Virally expressed AMPAR subunits (GluR1 or GluR2) accumulated in cell bodies and replaced endogenous dendritic AMPAR with little effect on total dendritic amounts and caused no change in synaptic transmission. Coexpressing stargazin (STG) or mimicking GluR1 phosphorylation enhanced dendritic GluR1 levels by protecting GluR1 from lysosomal degradation. However, STG interaction or GluR1 phosphorylation did not increase surface or synaptic GluR1 levels. Unlike GluR1, STG did not protect GluR2 from lysosomal degradation or increase dendritic GluR2 levels. In general, AMPAR surface levels, and not intracellular amounts, correlated strongly with synaptic levels. Our results suggest that AMPAR surface expression, but not its intracellular production or accumulation, is critical for regulating synaptic transmission.
1 Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.