Yang, W.K., Peng, Y.H., Li, H., Lin, H.C., Lin, Y.C., Lai, T.T., Suo, H., Wang, C.H., Lin, W.H., Ou, C.Y., Zhou, X., Pi, H., Chang, H.C., Chien, C.T. (2011). Nak regulates localization of clathrin sites in higher-order dendrites to promote local dendrite growth.  Neuron 72(2): 285--299.

FBrf0216477

Research paper

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.