Cited by 44Axon Guidance and Neuronal SignalingBone Metabolism and DiseasesCellular Mechanics and Interactions

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

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Deb Roy, Abhijit, Yin, Taofei, Choudhary, Shilpa, Rodionov, Vladimir, Pilbeam, Carol C., Wu, Yi I.·2017·Nature Communications

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, PIP 3, 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.

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Authors
Deb Roy, A., Yin, T., Choudhary, S., Rodionov, V., Pilbeam, C. C., & Wu, Y. I.
Affiliations
University of Connecticut (US)
Corresponding author
Wu, Yi I.
Venue
Nature Communications
Published
2017-06-21
Volume
8
Issue
1
Pages
15831-15831
ISSN
2041-1723 (ISSN-L)
OpenAlex
W2663175999
Cited by
44
References
70
Citations by year
2026: 4 · 2025: 3 · 2024: 7 · 2023: 2 · 2022: 6 · 2021: 9 · 2020: 7 · 2019: 2 · 2018: 3 · 2017: 1
FWCI
1.74
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institute of General Medical Sciences (R01GM117061, R01GM062290)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR060286)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords
Plexin-B1, Sema4D, contact inhibition of locomotion, osteoclasts, osteoblasts, bone remodeling, cell migration, optogenetic stimulation, Cdc42, RhoA/ROCK signaling, betaPIX, myosin II, phosphatidylinositol 3,4,5-trisphosphate, cell protrusions, chemotaxis
MeSH terms
Animals, Cell Movement, Light, Male, Mice, Inbred C57BL, Nerve Tissue Proteins, Osteoblasts, Osteoclasts, Receptors, Cell Surface, Signal Transduction, Cell Polarity, rhoA GTP-Binding Protein, cdc42 GTP-Binding Protein, Myosin Type II, Semaphorins, Mice, Optogenetics

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