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Optogenetic activation of Plexin-B1 reveals contact repulsion between osteoclasts and osteoblasts

Author

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  • Abhijit Deb Roy

    (Richard D. Berlin Center for Cell Analysis and Modeling, University of Connecticut School of Medicine)

  • Taofei Yin

    (Richard D. Berlin Center for Cell Analysis and Modeling, University of Connecticut School of Medicine)

  • Shilpa Choudhary

    (New England Musculoskeletal Institute, University of Connecticut School of Medicine)

  • Vladimir Rodionov

    (Richard D. Berlin Center for Cell Analysis and Modeling, University of Connecticut School of Medicine
    University of Connecticut School of Medicine)

  • Carol C. Pilbeam

    (New England Musculoskeletal Institute, University of Connecticut School of Medicine)

  • Yi I. Wu

    (Richard D. Berlin Center for Cell Analysis and Modeling, University of Connecticut School of Medicine
    University of Connecticut School of Medicine)

Abstract

During bone remodelling, osteoclasts induce chemotaxis of osteoblasts and yet maintain spatial segregation. We show that osteoclasts express the repulsive guidance factor Semaphorin 4D and induce contact inhibition of locomotion (CIL) in osteoblasts through its receptor Plexin-B1. To examine causality and elucidate how localized Plexin-B1 stimulation may spatiotemporally coordinate its downstream targets in guiding cell migration, we develop an optogenetic tool for Plexin-B1 designated optoPlexin. Precise optoPlexin activation at the leading edge of migrating osteoblasts readily induces local retraction and, unexpectedly, distal protrusions to steer cells away. These morphological changes are accompanied by reorganization of Myosin II, PIP3, adhesion and active Cdc42. We attribute the resultant repolarization to RhoA/ROCK-mediated redistribution of β-Pix, which activates Cdc42 and promotes protrusion. Thus, our data demonstrate a causal role of Plexin-B1 for CIL in osteoblasts and reveals a previously unknown effect of Semaphorin signalling on spatial distribution of an activator of cell migration.

Suggested Citation

  • Abhijit Deb Roy & Taofei Yin & Shilpa Choudhary & Vladimir Rodionov & Carol C. Pilbeam & Yi I. Wu, 2017. "Optogenetic activation of Plexin-B1 reveals contact repulsion between osteoclasts and osteoblasts," Nature Communications, Nature, vol. 8(1), pages 1-15, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15831
    DOI: 10.1038/ncomms15831
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    Cited by:

    1. Hideaki T. Matsubayashi & Jack Mountain & Nozomi Takahashi & Abhijit Deb Roy & Tony Yao & Amy F. Peterson & Cristian Saez Gonzalez & Ibuki Kawamata & Takanari Inoue, 2024. "Non-catalytic role of phosphoinositide 3-kinase in mesenchymal cell migration through non-canonical induction of p85β/AP2-mediated endocytosis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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