New methods to decrypt emerging macropinosome functions during the host–pathogen crosstalk

Cellular Microbiology, vol. 23, pp. e13342

Abstract

Large volumes of liquid and other materials from the extracellular environment are internalised by eukaryotic cells via an endocytic process called macropinocytosis. It is now recognised that this fundamental and evolutionarily conserved pathway is hijacked by numerous intracellular pathogens as an entry portal to the host cell interior. Yet, an increasing number of additional cellular functions of macropinosomes in pathologic processes have been reported beyond this role for fluid internalisation. It emerges that the identity of macropinosomes can vary hugely and change rapidly during their lifetime. A deeper understanding of this important multi-faceted compartment is based on novel methods for their investigation. These methods are either imaging-based for the tracking of macropinosome dynamics, or they provide the means to extract macropinosomes at high purity for comprehensive proteomic analyses. Here, we portray these new approaches for the investigation of macropinosomes. We document how these method developments have provided insights for a new understanding of the intracellular lifestyle of the bacterial pathogens Shigella and Salmonella. We suggest that a systematic complete characterisation of macropinosome subversion with these approaches during other infection processes and pathologies will be highly beneficial for our understanding of the underlying cellular and molecular processes.

Authors 3

1. Yuen‐Yan Chang corresponding

   Centre National de la Recherche Scientifique · National Institutes of Health · Institut Pasteur · Eunice Kennedy Shriver National Institute of Child Health and Human Development · Biologie cellulaire physiologique et pathologique

   Affiliation as printed

   Division of Molecular and Cellular Biology National Institute of Child Health and Human Development, NIH Bethesda Maryland USA

   Institut Pasteur Dynamics of Host‐Pathogen Interactions Unit and CNRS UMR 3691 Paris France

   Division of Molecular and Cellular Biology, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland, USA

   Institut Pasteur, Dynamics of Host-Pathogen Interactions Unit and CNRS UMR 3691, Paris, France

2. Jost Enninga

   Centre National de la Recherche Scientifique · Institut Pasteur · Biologie cellulaire physiologique et pathologique

   Affiliation as printed

   Institut Pasteur Dynamics of Host‐Pathogen Interactions Unit and CNRS UMR 3691 Paris France

   Institut Pasteur, Dynamics of Host-Pathogen Interactions Unit and CNRS UMR 3691, Paris, France

3. Virginie Stévenin corresponding Aachen Department of Cell & Chemical Biology Leiden University Medical Center Leiden Netherlands Department of Cell and Chemical Biology

   Centre National de la Recherche Scientifique · Université Paris Diderot · Institut Pasteur · Leiden University Medical Center · Biologie cellulaire physiologique et pathologique

   Affiliation as printed

   Department of Cell and Chemical Biology Leiden University Medical Center Leiden Netherlands

   Institut Pasteur Dynamics of Host‐Pathogen Interactions Unit and CNRS UMR 3691 Paris France

   Université Paris Diderot Ecole doctorale BioSPC Paris France

   Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands

   Institut Pasteur, Dynamics of Host-Pathogen Interactions Unit and CNRS UMR 3691, Paris, France