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.
Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
Wei-Kang
WK
Yang
Yu-Huei
YH
Peng
Hsun
H
Li
Hsiu-Chen
HC
Lin
Yu-Ching
YC
Lin
Tzu-Ting
TT
Lai
Hsien
H
Suo
Chien-Hsiang
CH
Wang
Wei-Hsiang
WH
Lin
Chan-Yen
CY
Ou
Xin
X
Zhou
Haiwei
H
Pi
Henry C
HC
Chang
Cheng-Ting
CT
Chien
D000818:Animals; D030801:Animals, Genetically Modified; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
D015816:Cell Adhesion Molecules, Neuronal; D002966:Clathrin; D029721:Drosophila Proteins; C061745:Nrg protein, Drosophila; C109770:Nak protein, Drosophila; D017346:Protein Serine-Threonine Kinases