Saglietti Laura, Dequidt Caroline, Kamieniarz Kinga, Rousset Marie-Claude, Valnegri Pamela, Thoumine Olivier, Beretta Francesca, Fagni Laurent, Choquet Daniel, Sala Carlo, Sheng Morgan, Passafaro Maria
DTI Dulbecco Telethon Institute, CNR Institute of Neuroscience, Cellular and Molecular Pharmacology, Department of Pharmacology, University of Milan, Italy.
Neuron. 2007 May 3;54(3):461-77. doi: 10.1016/j.neuron.2007.04.012.
Via its extracellular N-terminal domain (NTD), the AMPA receptor subunit GluR2 promotes the formation and growth of dendritic spines in cultured hippocampal neurons. Here we show that the first N-terminal 92 amino acids of the extracellular domain are necessary and sufficient for GluR2's spine-promoting activity. Moreover, overexpression of this extracellular domain increases the frequency of miniature excitatory postsynaptic currents (mEPSCs). Biochemically, the NTD of GluR2 can interact directly with the cell adhesion molecule N-cadherin, in cis or in trans. N-cadherin-coated beads recruit GluR2 on the surface of hippocampal neurons, and N-cadherin immobilization decreases GluR2 lateral diffusion on the neuronal surface. RNAi knockdown of N-cadherin prevents the enhancing effect of GluR2 on spine morphogenesis and mEPSC frequency. Our data indicate that in hippocampal neurons N-cadherin and GluR2 form a synaptic complex that stimulates presynaptic development and function as well as promoting dendritic spine formation.
通过其细胞外N端结构域（NTD），AMPA受体亚基GluR2促进培养的海马神经元中树突棘的形成和生长。在此我们表明，细胞外结构域的首个N端92个氨基酸对于GluR2的棘突促进活性是必要且充分的。此外，该细胞外结构域的过表达增加了微小兴奋性突触后电流（mEPSCs）的频率。在生化方面，GluR2的NTD可以顺式或反式与细胞粘附分子N-钙粘蛋白直接相互作用。N-钙粘蛋白包被的珠子在海马神经元表面募集GluR2，并且N-钙粘蛋白的固定减少了GluR2在神经元表面的横向扩散。RNA干扰敲低N-钙粘蛋白可阻止GluR2对棘突形态发生和mEPSC频率的增强作用。我们的数据表明，在海马神经元中，N-钙粘蛋白和GluR2形成一个突触复合体，该复合体刺激突触前发育和功能以及促进树突棘形成。
