AMPA受體是人類神經(jīng)細(xì)胞連接之間的重要調(diào)控因子,。但荷蘭研究人員Helmut Kessels發(fā)現(xiàn),，AMPA受體功能的發(fā)揮與細(xì)胞內(nèi)AMPA受體的數(shù)量無關(guān)，而與該受體在細(xì)胞膜上的位置有關(guān),。因此,，僅僅增加細(xì)胞內(nèi)的AMPA受體的數(shù)量并不足以調(diào)節(jié)神經(jīng)細(xì)胞之間的連接,。神經(jīng)細(xì)胞之間的連接能夠影響我們的學(xué)習(xí)能力,。
這項(xiàng)研究發(fā)表在9月版的Nature Neuroscience雜志上,。
AMPA受體影響突觸可塑性(synaptic plasticity)——即兩個(gè)神經(jīng)細(xì)胞連接(突觸)的強(qiáng)度改變的能力。之前有研究認(rèn)為,，細(xì)胞內(nèi)AMPA受體的數(shù)量能夠引起神經(jīng)細(xì)胞的連接,，從而影響我們的學(xué)習(xí)能力。
雖然細(xì)胞內(nèi)能夠產(chǎn)生大量的AMPA受體,，但大部分都被溶酶體所降解,。Kessels對AMPA受體兩個(gè)亞基——GluR1 和GluR2進(jìn)行研究，這兩個(gè)亞基對我們學(xué)習(xí)能力有不同的影響,。GluR1對新記憶的形成至關(guān)重要,，GluR2在記憶儲(chǔ)存上具有重要作用。
研究人員通過增加與GluR1相同數(shù)量的受體相互作用蛋白stargazin來阻止溶酶體降解GluR1,，磷酸化GluR1也能獲得同樣的效果,。然而研究人員發(fā)現(xiàn)，細(xì)胞內(nèi)GluR1數(shù)量的增加并未增加細(xì)胞內(nèi)受體的數(shù)量,，也未增加突觸的數(shù)量,。對GluR2的研究也產(chǎn)生了相同的結(jié)果。該結(jié)論還需要進(jìn)一步證實(shí)是否受體的位置的確可以影響突觸可塑性以及我們學(xué)習(xí)的能力,。(生物谷Bioon.com)
生物谷推薦原始出處：
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.
