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Published March 14, 2016 | Published + Supplemental Material
Journal Article Open

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

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.

Additional Information

© 2016, Dong et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. Received August 20, 2015. Accepted February 26, 2016. Published March 14, 2016. This work was supported by the Howard Hughes Medical Institute and by NIH (1R01NS082208-01A1) to KS, by NIH (5R01GM111320) and by NSF (IOS-1455758) to C Chang. The work in the Özkan's lab was supported by a Klingenstein-Simons Fellowship in the Neuroscience. We thank the Caenorhabditis Genetics Center for the kpc-1(gk8) strain, the laboratories of L Luo and M Scott for Drosophila S2 and S2R+ cell lines, CG Fernandez for the GPR56 protein, and M Snyder for allowing us to use the FastPrep equipment. We also thank C Richardson for critical reading of the manuscript. Author contributions: XD, Conception and design, Acquisition of data, Analysis and interpretation of data, Drafting or revising the article. HC, Acquisition of data, Contributed unpublished essential data or reagents. YJP, Designed and performed the experiments shown in Figure 7F, Acquisition of data, Analysis and interpretation of data, Drafting or revising the article. WZ, Drafting or revising the article, Contributed unpublished essential data or reagents. YZ, Acquisition of data, Contributed unpublished essential data or reagents. EÖ, Designed and performed the experiments shown in Figure 7F, Acquisition of data, Analysis and interpretation of data, Drafting or revising the article. CC, Conception and design, Drafting or revising the article. Contributed unpublished essential data or reagents. KS, Conception and design, Analysis and interpretation of data, Drafting or revising the article. Competing interests: KS: Reviewing editor, eLife. The other authors declare that no competing interests exist. Funding Howard Hughes Medical Institute: Xintong Dong ,Wei Zou, Kang Shen. National Institutes of Health 1R01NS082208-01A1: Xintong Dong, Wei Zou, Kang Shen. National Institutes of Health 5R01GM111320: Hui Chiu, Yan Zou, Chieh Chang. National Science Foundation: Hui Chiu, Yan Zou, Chieh Chang. Esther A. and Joseph Klingenstein Fund: Yeonhee Jenny Park, Engin Özkan. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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August 20, 2023
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October 18, 2023