Interaction between telencephalin and ERM family proteins mediates dendritic filopodia formation
Interaction between telencephalin and ERM family proteins mediates dendritic filopodia formation
复制标题
DOI：
10.1523/jneurosci.1047-07.2007
复制
发表时间：
2007-08-15
影响因子：
5.3
通讯作者：
Yoshihara, Yoshihiro
中科院分区：
文献类型：
--
作者：
Furutani, Yutaka;Matsuno, Hitomi;Yoshihara, Yoshihiro
树突状丝状伪足是一种长而细、富含肌动蛋白的动态突起，被认为在神经发育过程中作为棘的前体起着关键作用。我们以前报道过，端脑特异性细胞粘附分子，端脑蛋白（TLCN）[细胞间粘附分子-5（ICAM-5）]，在树突状丝状伪足中高度表达，促进丝状伪足的形成，并减缓棘成熟。在这里，我们证明了TLCN细胞质区域结合ERM（埃兹蛋白/根蛋白/膜突蛋白）家族蛋白，该家族蛋白将膜蛋白连接到肌动蛋白细胞骨架。在培养的海马神经元中，磷酸化的活性形式的ERM蛋白与TLCN共定位在树突丝状伪足中，而α-辅肌动蛋白，TLCN的另一种结合伴侣，与TLCN共定位在索马和树突轴的表面膜上。组成型活性ezrin的表达诱导树突状丝状伪足形成，而小干扰RNA介导的ERM蛋白敲低降低丝状伪足密度并加速棘成熟。这些结果表明TLCN-ERM相互作用在树突状丝状伪足的形成中的重要作用，其导致随后的突触发生和发育中的大脑中功能性神经回路的建立。
Dendritic filopodia are long, thin, actin-rich, and dynamic protrusions that are thought to play a critical role as a precursor of spines during neural development. We reported previously that a telencephalon-specific cell adhesion molecule, telencephalin (TLCN) [intercellular adhesion molecule-5 (ICAM-5)], is highly expressed in dendritic filopodia, facilitates the filopodia formation, and slows spine maturation. Here we demonstrate that TLCN cytoplasmic region binds ERM (ezrin/radixin/moesin) family proteins that link membrane proteins to actin cytoskeleton. In cultured hippocampal neurons, phosphorylated active forms of ERM proteins are colocalized with TLCN in dendritic filopodia, whereas alpha-actinin, another binding partner of TLCN, is colocalized with TLCN at surface membranes of soma and dendritic shafts. Expression of constitutively active ezrin induces dendritic filopodia formation, whereas small interference RNA-mediated knockdown of ERM proteins decreases filopodia density and accelerates spine maturation. These results indicate the important role of TLCN-ERM interaction in the formation of dendritic filopodia, which leads to subsequent synaptogenesis and establishment of functional neural circuitry in the developing brain.