Department of Cell and Molecular Physiology and Neuroscience Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
PLoS One. 2011;6(9):e24335. doi: 10.1371/journal.pone.0024335. Epub 2011 Sep 6.
Conditional deletion of APC leads to marked disruption of cortical development and to excessive axonal branching of cortical neurons. However, little is known about the cell biological basis of this neuronal morphological regulation. Here we show that APC deficient cortical neuronal growth cones exhibit marked disruption of both microtubule and actin cytoskeleton. Functional analysis of the different APC domains revealed that axonal branches do not result from stabilized β-catenin, and that the C-terminus of APC containing microtubule regulatory domains only partially rescues the branching phenotype. Surprisingly, the N-terminus of APC containing the oligomerization domain and the armadillo repeats completely rescues the branching and cytoskeletal abnormalities. Our data indicate that APC is required for appropriate axon morphological development and that the N-terminus of APC is important for regulation of the neuronal cytoskeleton.
条件性敲除 APC 会导致皮质发育明显中断，并导致皮质神经元的轴突分支过度生长。然而，对于这种神经元形态调节的细胞生物学基础知之甚少。在这里，我们表明 APC 缺陷的皮质神经元生长锥表现出微管和肌动蛋白细胞骨架的明显破坏。对 APC 的不同结构域的功能分析表明，轴突分支不是由稳定的β-连环蛋白引起的，并且仅包含微管调节结构域的 APC C 端部分挽救了分支表型。令人惊讶的是，含有寡聚化结构域和装甲重复的 APC N 端完全挽救了分支和细胞骨架异常。我们的数据表明，APC 是适当的轴突形态发育所必需的，并且 APC 的 N 端对于神经元细胞骨架的调节很重要。
