Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
Neuron. 2011 Oct 20;72(2):285-99. doi: 10.1016/j.neuron.2011.08.028.
During development, dendrites arborize in a field several hundred folds of their soma size, a process regulated by intrinsic transcription program and cell adhesion molecule (CAM)-mediated interaction. However, underlying cellular machineries that govern distal higher-order dendrite extension remain largely unknown. Here, we show that Nak, a clathrin adaptor-associated kinase, promotes higher-order dendrite growth through endocytosis. In nak mutants, both the number and length of higher-order dendrites are reduced, which are phenocopied by disruptions of clathrin-mediated endocytosis. Nak interacts genetically with components of the endocytic pathway, colocalizes with clathrin puncta, and is required for dendritic localization of clathrin puncta. More importantly, these Nak-containing clathrin structures preferentially localize to branching points and dendritic tips that are undergoing active growth. We present evidence that the Drosophila L1-CAM homolog Neuroglian is a relevant cargo of Nak-dependent internalization, suggesting that localized clathrin-mediated endocytosis of CAMs facilitates the extension of nearby higher-order dendrites.
在发育过程中，树突分枝的范围是其胞体大小的几百倍，这一过程受到内在转录程序和细胞黏附分子（CAM）介导的相互作用的调节。然而，控制远端高级树突延伸的细胞机制在很大程度上仍然未知。在这里，我们表明 Nak（网格蛋白衔接蛋白相关激酶）通过内吞作用促进高级树突生长。在 nak 突变体中，高级树突的数量和长度都减少了，这与网格蛋白介导的内吞作用的破坏所产生的表型相似。Nak 在遗传上与内吞作用途径的成分相互作用，与网格蛋白斑点共定位，并需要网格蛋白斑点在树突上的定位。更重要的是，这些含有 Nak 的网格蛋白结构优先定位于正在进行活跃生长的分支点和树突尖端。我们提出的证据表明，果蝇 L1-CAM 同源物 Neuroglian 是 Nak 依赖性内化的相关货物，这表明局部网格蛋白介导的 CAM 内吞作用促进了附近高级树突的延伸。
