Gong Liang-Wei, De Camilli Pietro
Department of Cell Biology, Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06510, USA.
Proc Natl Acad Sci U S A. 2008 Nov 11;105(45):17561-6. doi: 10.1073/pnas.0809221105. Epub 2008 Nov 5.
Endocytosis of postsynaptic AMPA receptors is a mechanism through which efficiency of neurotransmission is regulated. We have genetically tested the hypothesis that synaptojanin 1, a phosphoinositide phosphatase implicated in the endocytosis of synaptic vesicles presynaptically, may also function in the endocytosis of AMPA receptors postsynaptically. Electrophysiological recordings of cultured hippocampal neurons showed that miniature excitatory postsynaptic current amplitudes were larger in synaptojanin 1 knockout (KO) neurons because of an increase of surface-exposed AMPA receptors. This change did not represent an adaptive response to decreased presynaptic release in KO cultures and was rescued by the expression of wild type, but not catalytically inactive synaptojanin 1, in the postsynaptic neuron. NMDA-induced internalization of pHluorin-tagged AMPA receptors (GluR2) was impaired in KO neurons. These results reveal a function of synaptojanin 1 in constitutive and triggered internalization of AMPA receptors and thus indicate a role for phosphatidylinositol(4,5)-bisphosphate metabolism in the regulation of postsynaptic AMPA responses.
突触后AMPA受体的内吞作用是一种调节神经传递效率的机制。我们通过遗传学方法验证了以下假说：突触素1（一种与突触前突触小泡内吞作用有关的磷酸肌醇磷酸酶）可能在突触后AMPA受体的内吞作用中也发挥作用。对培养的海马神经元进行电生理记录显示，由于表面暴露的AMPA受体增加，突触素1基因敲除（KO）神经元中的微小兴奋性突触后电流幅度更大。这种变化并非对KO培养物中突触前释放减少的适应性反应，并且通过在突触后神经元中表达野生型而非催化失活的突触素1得以挽救。NMDA诱导的pHluorin标记的AMPA受体（GluR2）的内化在KO神经元中受损。这些结果揭示了突触素1在AMPA受体组成性和触发式内化中的作用，从而表明磷脂酰肌醇（4,5）-二磷酸代谢在调节突触后AMPA反应中的作用。
