Integrin-based diffusion barrier separates membrane domains enabling formation of microbiostatic frustrated phagosomes
- The Hospital for Sick Children, Canada
- University Medical Center Hamburg-Eppendorf, Germany
- University of Toronto, Canada
Abstract
Candida albicans hyphae can reach enormous lengths, precluding their internalization by phagocytes. Nevertheless, macrophages engulf a portion of the hypha, generating incompletely sealed tubular phagosomes. These frustrated phagosomes are stabilized by a thick cuff of F-actin that polymerizes in response to non-canonical activation of integrins by fungal glycan. Despite their continuity, the surface and invaginating phagosomal membranes retain a strikingly distinct lipid composition. PtdIns(4,5)P2 is present at the plasmalemma but is not detectable in the phagosomal membrane, while PtdIns(3)P and PtdIns(3,4,5)P3 co-exist in the phagosomes yet are absent from the surface membrane. Moreover, endo-lysosomal proteins are present only in the phagosomal membrane. Fluorescence recovery after photobleaching revealed the presence of a diffusion barrier that maintains the identity of the open tubular phagosome separate from the plasmalemma. Formation of this barrier depends on Syk, Pyk2/Fak and formin-dependent actin assembly. Antimicrobial mechanisms can thereby be deployed, limiting the growth of the hyphae.
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Author details
Funding
Canadian Institutes of Health Research (FDN‑143202)
- Sergio Grinstein
Natural Sciences and Engineering Research Council of Canada (462167)
- Leah E Cowen
Canadian Institutes of Health Research (PJT-148548)
- Leah E Cowen
Canadian Institutes of Health Research (MOP-86452)
- Leah E Cowen
Canadian Institutes of Health Research (MOP-119520)
- Leah E Cowen
Heart and Stroke Foundation of Canada (Heart and Stroke Pfizer Fellowship)
- Michelle E Maxson
National Institutes of Health (AI115947-01)
- Teresa R O'Meara
The Research Training Group 1459
- Xenia Naj
Natural Sciences and Engineering Research Council of Canada (6261)
- Leah E Cowen
Canadian Institutes of Health Research (FDN-154288)
- Leah E Cowen
Canadian Institutes of Health Research (PJT-153403)
- Leah E Cowen
National Institutes of Health (1R01AI127375-01)
- Leah E Cowen
Natural Sciences and Engineering Research Council of Canada (477598)
- Leah E Cowen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Maxson et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Integrin-based diffusion barrier separates membrane domains enabling formation of microbiostatic frustrated phagosomes
eLife 7:e34798.
https://doi.org/10.7554/eLife.34798
