Dynamin participates in focal extracellular matrix degradation by invasive cells

Massimiliano Baldassarre, Arsenio Pompeo, Galina Beznoussenko, Claudia Castaldi, Salvatore Cortellino, Mark A. McNiven, Alberto Luini, Roberto Buccione

Research output: Contribution to journalArticle

159 Scopus citations

Abstract

The degradation of extracellular matrix (ECM) by matrix metalloproteases is crucial in physiological and pathological cell invasion alike. Degradation occurs at specific sites where invasive I cells make contact with the ECM via specialized plasma membrane protrusions termed invadopodia. Herein, we show that the dynamin 2 (Dyn2), a GTPase implicated in the control of actindriven cytoskeletal remodeling events and membrane transport, is necessary for focalized matrix degradation at invadopodia. Dynamin was inhibited by using two approaches: 1) expression of dominant negative GTPase-impaired or proline-rich domain-deleted Dyn2 mutants; and 2) inhibition of the dynamin regulator calcineurin by cyclosporin A. In both cases, the number and extension of ECM degradation foci were drastically reduced. To understand the site and mechanism of dynamin action, the cellular structures devoted to ECM degradation were analyzed by correlative confocal light-electron microscopy. Invadopodia were found to be organized into a previously undescribed ECM-degradation structure consisting of a large invagination of the ventral plasma membrane surface in close spatial relationship with the Golgi complex. Dyn2 seemed to be concentrated at invadopodia.

Original languageEnglish (US)
Pages (from-to)1074-1084
Number of pages11
JournalMolecular biology of the cell
Volume14
Issue number3
DOIs
StatePublished - Mar 1 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Baldassarre, M., Pompeo, A., Beznoussenko, G., Castaldi, C., Cortellino, S., McNiven, M. A., Luini, A., & Buccione, R. (2003). Dynamin participates in focal extracellular matrix degradation by invasive cells. Molecular biology of the cell, 14(3), 1074-1084. https://doi.org/10.1091/mbc.E02-05-0308