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PLoS One. 2013 Dec 9;8(12):e77956. doi: 10.1371/journal.pone.0077956. eCollection 2013.

Essential function of dynamin in the invasive properties and actin architecture of v-Src induced podosomes/invadosomes.

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  • 1Institut Albert Bonniot, Université Joseph Fourier; Université Joseph Fourier site Santé, Grenoble cedex, France ; Department of Cell Biology, Howard Hughes Medical Institute, Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, Connecticut, United States of America.
  • 2Department of Cell Biology, Howard Hughes Medical Institute, Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, Connecticut, United States of America.
  • 3Institut Albert Bonniot, Université Joseph Fourier; Université Joseph Fourier site Santé, Grenoble cedex, France.
  • 4Department of Cell Biology, Howard Hughes Medical Institute, Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, Connecticut, United States of America ; Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, United States of America.
  • 5Institut Albert Bonniot, Université Joseph Fourier; Université Joseph Fourier site Santé, Grenoble cedex, France ; Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, United States of America.
  • 6Department of Medicine, Harvard Medical School, Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, United States of America.

Abstract

The large GTPase dynamin plays a key role in endocytosis but is also localized at numerous actin rich sites. We investigated dynamin functions at podosomes/invadosomes, actin-based cellular adhesion structures implicated in tissue invasion. Podosomes/invadosomes are constituted of long F-actin bundles perpendicular to the substratum (actin cores), connected to randomly arranged F-actin fibers parallel to the substratum (actin cloud). We show here that dynamin depletion in v-Src-transformed fibroblasts triggers a massive disorganization of podosomes/invadosomes (isolated or in rosettes), with a corresponding inhibition of their invasive properties. The action of dynamin at podosomes/invadosomes requires a functional full-length protein, suggesting that the effects of dynamin at these sites and in membrane remodelling during endocytosis are mediated by similar mechanisms. In order to determine direct effect of dynamin depletion on invadosome, an optogenetic approach based on the photosensitizer KillerRed was developed. Acute dynamin photo-inactivation leads to a very rapid disorganization of invadosome without affecting focal adhesions. Dynamin therefore is a key regulator of the architecture of actin in podosomes/invadosomes.

PMID:
24348990
[PubMed - indexed for MEDLINE]
PMCID:
PMC3857171
Free PMC Article
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