SynDIG1: an activity-regulated, AMPA- receptor-interacting transmembrane protein that regulates excitatory synapse development.
SynDIG1: an activity-regulated, AMPA- receptor-interacting transmembrane protein that regulates excitatory synapse development.
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DOI：
10.1016/j.neuron.2009.12.021
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发表时间：
2010-01-14
期刊：
影响因子：
16.2
通讯作者：
Diaz, Elva
中科院分区：
文献类型：
--
作者：
Kalashnikova, Evgenia;Lorca, Ramon A.;Kaur, Inderpreet;Barisone, Gustavo A.;Li, Bonnie;Ishimaru, Tatsuto;Trimmer, James S.;Mohapatra, Durga P.;Diaz, Elva
在中枢神经系统的发育过程中，突触前和突触后神经元之间形成了精确的突触连接。虽然我们对突触可塑性过程中AMPA受体运输的理解已经取得了重大进展，但在突触发生过程中将AMPA受体招募到新生突触的分子知之甚少。在这里，我们发现了一种II型跨膜蛋白（SynDIG1），它可以调节游离大鼠海马神经元发育突触中的AMPA受体含量。SynDIG1在突触和突触外与AMPA受体共定位，并在异源细胞和大脑中与AMPA受体结合。在培养的神经元中SynDIG1水平的改变导致兴奋性突触数量和功能的显著变化。syndig1介导的突触发育依赖于通过其细胞外c端与AMPA受体的关联。有趣的是，树突棘中的SynDIG1含量受神经元活动的调节。总之，我们将SynDIG1定义为一种调节兴奋性突触发育的活性调节跨膜蛋白。
During development of the central nervous system, precise synaptic connections between pre- and postsynaptic neurons are formed. While significant progress has been made in our understanding of AMPA receptor trafficking during synaptic plasticity, less is known about the molecules that recruit AMPA receptors to nascent synapses during synaptogenesis. Here we identify a type II transmembrane protein (SynDIG1) that regulates AMPA receptor content at developing synapses in dissociated rat hippocampal neurons. SynDIG1 colocalizes with AMPA receptors at synapses and at extra-synaptic sites and associates with AMPA receptors in heterologous cells and brain. Altered levels of SynDIG1 in cultured neurons result in striking changes in excitatory synapse number and function. SynDIG1-mediated synapse development is dependent on association with AMPA receptors via its extracellular C-terminus. Intriguingly, SynDIG1 content in dendritic spines is regulated by neuronal activity. Altogether, we define SynDIG1 as an activity-regulated transmembrane protein that regulates excitatory synapse development.
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