Published on: Neuron Volume 72, Issue 2, 20 October 2011, Pages 285–299

Nak Regulates Localization of Clathrin Sites in Higher-Order Dendrites to Promote Local Dendrite Growth


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.


► Nak facilitates endocytosis to regulate higher-order dendrite growth ► Nak colocalizes with and directs the dendritic localization of distal clathrin puncta ► The Nak/clathrin puncta promote local dendrite growth ► Neuroglian/L1 is a relevant cargo of Nak-dependent endocytosis in dendrite growth