Interplay between myosin IIA-mediated contractility and actin network integrity orchestrates podosome composition and oscillations

K van den Dries, M B M Meddens, T.J.S. Keijzer, Shashank Shekhar, V Subramaniam, Carl G Figdor, A. Cambi

    Research output: Contribution to JournalArticleAcademicpeer-review

    Abstract

    Tissue-resident dendritic cells patrol for foreign antigens while undergoing slow mesenchymal migration. Using actomyosin-based structures called podosomes, dendritic cells probe and remodel extracellular matrix topographical cues. Podosomes comprise an actin-rich protrusive core surrounded by an adhesive ring of integrins, cytoskeletal adaptor proteins and actin network filaments. Here we reveal how the integrity and dynamics of protrusive cores and adhesive rings are coordinated by the actomyosin apparatus. Core growth by actin polymerization induces podosome protrusion and provides tension within the actin network filaments. The tension transmitted to the ring recruits vinculin and zyxin and preserves overall podosome integrity. Conversely, myosin IIA contracts the actin network filaments and applies tension to the vinculin molecules bound, counterbalancing core growth and eventually reducing podosome size and protrusion. We demonstrate a previously unrecognized interplay between actin and myosin IIA in podosomes, providing novel mechanistic insights into how actomyosin-based structures allow dendritic cells to sense the extracellular environment.

    Original languageEnglish
    Pages (from-to)1412
    JournalNature Communications
    Volume4
    DOIs
    Publication statusPublished - 2013

    Keywords

    • Actins
    • Cytoplasmic Structures
    • Dendritic Cells
    • Focal Adhesions
    • Green Fluorescent Proteins
    • Humans
    • Models, Biological
    • Nonmuscle Myosin Type IIA
    • Polymerization
    • Transfection
    • Vinculin
    • Zyxin
    • Journal Article
    • Research Support, Non-U.S. Gov't

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