Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan.
Mol Biol Cell. 2012 Nov;23(22):4383-92. doi: 10.1091/mbc.E12-05-0365. Epub 2012 Sep 26.
Cortactin-binding protein 2 (CTTNBP2) interacts with cortactin to regulate cortactin mobility and control dendritic spine formation. CTTNBP2 has also been associated with autistic spectrum disorder. The regulation of dendritic spinogenesis could explain the association of CTTNBP2 with autism. Sequence comparison has indicated that CTTNBP2 N-terminal-like protein (CTTNBP2NL) is a CTTNBP2 homologue. To confirm the specific effect of CTTNBP2 on dendritic spinogenesis, here we investigate whether CTTNBP2NL has a similar function to CTTNBP2. Although both CTTNBP2 and CTTNBP2NL interact with cortactin, CTTNBP2NL is associated with stress fibers, whereas CTTNBP2 is distributed to the cortex and intracellular puncta. We also provide evidence that CTTNBP2, but not CTTNBP2NL, is predominantly expressed in the brain. CTTNBP2NL does not show any activity in the regulation of dendritic spinogenesis. In addition to spine morphology, CTTNBP2 is also found to regulate the synaptic distribution of striatin and zinedin (the regulatory B subunits of protein phosphatase 2A [PP2A]), which interact with CTTNBP2NL in HEK293 cells. The association between CTTNBP2 and striatin/zinedin suggests that CTTNBP2 targets the PP2A complex to dendritic spines. Thus we propose that the interactions of CTTNBP2 and cortactin and the PP2A complex regulate spine morphogenesis and synaptic signaling.
衔接蛋白结合蛋白 2（CTTNBP2）与衔接蛋白相互作用，调节衔接蛋白的迁移，控制树突棘的形成。CTTNBP2 也与自闭症谱系障碍有关。树突棘生成的调节可以解释 CTTNBP2 与自闭症的关联。序列比较表明，CTTNBP2N 端样蛋白（CTTNBP2NL）是 CTTNBP2 的同源物。为了证实 CTTNBP2 对树突棘生成的确切影响，我们研究了 CTTNBP2NL 是否具有与 CTTNBP2 相似的功能。尽管 CTTNBP2 和 CTTNBP2NL 都与衔接蛋白相互作用，但 CTTNBP2NL 与应激纤维相关，而 CTTNBP2 则分布在皮质和细胞内斑点中。我们还提供了证据表明，CTTNBP2 而不是 CTTNBP2NL，主要在大脑中表达。CTTNBP2NL 不会对树突棘生成的调节产生任何影响。除了棘突形态外，CTTNBP2 还被发现调节蛋白磷酸酶 2A（PP2A）的调节 B 亚基 striatin 和 zinedin 的突触分布，它们在 HEK293 细胞中与 CTTNBP2NL 相互作用。CTTNBP2 与 striatin/zinedin 的关联表明，CTTNBP2 将 PP2A 复合物靶向树突棘。因此，我们提出 CTTNBP2 与衔接蛋白的相互作用以及 PP2A 复合物调节棘突形态发生和突触信号传递。
