Furutani Yutaka, Matsuno Hitomi, Kawasaki Miwa, Sasaki Takehiko, Mori Kensaku, Yoshihara Yoshihiro
Laboratory for Neurobiology of Synapse, RIKEN Brain Science Institute, Saitama, Japan.
J Neurosci. 2007 Aug 15;27(33):8866-76. doi: 10.1523/JNEUROSCI.1047-07.2007.
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.
树突状丝状伪足是长而细、富含肌动蛋白且动态变化的突起，被认为在神经发育过程中作为棘突的前体发挥关键作用。我们之前报道过，一种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，促进丝状伪足形成，并减缓棘突成熟。在此我们证明，TLCN细胞质区域与将膜蛋白连接到肌动蛋白细胞骨架的ERM（埃兹蛋白/根蛋白/膜突蛋白）家族蛋白结合。在培养的海马神经元中，ERM蛋白的磷酸化活性形式与TLCN在树突状丝状伪足中共定位，而TLCN的另一个结合伴侣α - 辅肌动蛋白则与TLCN在胞体和树突轴的表面膜中共定位。组成型活性埃兹蛋白的表达诱导树突状丝状伪足形成，而小干扰RNA介导的ERM蛋白敲低降低了丝状伪足密度并加速了棘突成熟。这些结果表明TLCN - ERM相互作用在树突状丝状伪足形成中的重要作用，这导致发育中的大脑随后发生突触形成和功能性神经回路的建立。
