Dynamic Podosome-Like Structures in Nascent Phagosomes Are Coordinated by Phosphoinositides

Philip P. Ostrowski, Spencer A. Freeman, Gregory Fairn, Sergio Grinstein

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

Phagocytosis, the engulfment of particulate matter, requires the coordinated polymerization of F-actin; however, the nature and dynamics of the F-actin structures generated during the process are incompletely defined. Using super-resolution microscopy, we observed the formation of podosome-like structures during Fc receptor-mediated phagocytosis. Unlike conventional podosomes, these structures are short lived and vectorial, expanding radially from the sites where phagocytic targets are initially engaged. The expanding ring of podosome-like structures requires the localized formation of PtdIns(3,4,5)P3. Concomitantly, the initial podosome-like structures disappear from the center of the phagocytic cup, enabling membrane bending around the target. This coordinated disappearance is mediated by localized hydrolysis of PtdIns(4,5)P2 at the center of the cup. Interference reflection microscopy revealed that the podosome-like structures attach tightly to the target, facilitating the progressive engagement and activation of phagocytic receptors, creating a diffusion barrier and serving as support for the extension of exploratory lamellipodia that probe the target surface.

Original languageEnglish
Pages (from-to)397-410.e3
JournalDevelopmental Cell
Volume50
Issue number4
DOIs
Publication statusPublished - Aug 19 2019
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by a Studentship from the Canadian Institutes of Health Research (CIHR) to P.P.O. and by grant FDN-143202 from CIHR to S.G.

Publisher Copyright:
© 2019 Elsevier Inc.

ASJC Scopus Subject Areas

  • Molecular Biology
  • General Biochemistry,Genetics and Molecular Biology
  • Developmental Biology
  • Cell Biology

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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Ostrowski, P. P., Freeman, S. A., Fairn, G., & Grinstein, S. (2019). Dynamic Podosome-Like Structures in Nascent Phagosomes Are Coordinated by Phosphoinositides. Developmental Cell, 50(4), 397-410.e3. https://doi.org/10.1016/j.devcel.2019.05.028