Precise regulation of the guidance receptor DMA-1 by KPC-1/Furin instructs dendritic branching decisions

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Abstract

Extracellular adhesion molecules and their neuronal receptors guide the growth and branching of axons and dendrites. Growth cones are attracted to intermediate targets, but they must switch their response upon arrival so that they can move away and complete the next stage of growth. Here, we show that KPC-1, a C. elegans Furin homolog, regulates the level of the branching receptor DMA-1 on dendrites by targeting it to late endosomes. In kpc-1 mutants, the level of DMA-1 is abnormally high on dendrites, resulting in trapping of dendrites at locations where a high level of the cognate ligand, the adhesion molecule SAX-7/L1, is present. The misregulation of DMA-1 also causes dendritic self-avoidance defects. Thus, precise regulation of guidance receptors creates flexibility of responses to guidance signals and is critical for neuronal morphogenesis.

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Xintong Dong

Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States

Competing interests
No competing interests declared.
Hui Chiu

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States

Competing interests
No competing interests declared.
Yeonhee Jenny Park

Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, United States

Competing interests
No competing interests declared.
Wei Zou

Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States

Competing interests
No competing interests declared.
Yan Zou

School of Life Science, Shanghai Tech University, Shanghai, China

Competing interests
No competing interests declared.
Engin Özkan

Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, United States

Competing interests
No competing interests declared.
Chieh Chang

Department of Biological Sciences, University of Illinois at Chicago, Chicago, United States

Competing interests
No competing interests declared.
Kang Shen

Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States

For correspondence
kangshen@stanford.edu

Competing interests
Kang Shen, Reviewing editor, eLife.

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