title: RAB-5- and RAB-11-dependent vesicle-trafficking pathways are required for plasma membrane repair after attack by bacterial pore-forming toxin.
abstract: Pore-forming toxins (PFTs) secreted by pathogenic bacteria are the most common bacterial protein toxins and are important virulence factors for infection. PFTs punch holes in host cell plasma membranes, and although cells can counteract the resulting membrane damage, the underlying mechanisms at play remain unclear. Using Caenorhabditis elegans as a model, we demonstrate in vivo and in an intact epithelium that intestinal cells respond to PFTs by increasing levels of endocytosis, dependent upon RAB-5 and RAB-11, which are master regulators of endocytic and exocytic events. Furthermore, we find that RAB-5 and RAB-11 are required for protection against PFT and to restore integrity to the plasma membrane. One physical mechanism involved is the RAB-11-dependent expulsion of microvilli from the apical side of the intestinal epithelial cells. Specific vesicle-trafficking pathways thus protect cells against an attack by PFTs on plasma membrane integrity, via altered plasma membrane dynamics.
authors.affiliation: Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, 92093-0322, USA.
authors.forename: Ferdinand C O
authors.initials: FC
authors.lastname: Los
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Kao
authors.forename: Jane
authors.initials: J
authors.lastname: Smitham
authors.forename: Kent L
authors.initials: KL
authors.lastname: McDonald
authors.forename: Christine
authors.initials: C
authors.lastname: Ha
authors.forename: Christina A
authors.initials: CA
authors.lastname: Peixoto
authors.forename: Raffi V
authors.initials: RV
authors.lastname: Aroian
mesh_terms: D000818:Animals; D001419:Bacteria / Q000378:metabolism*; D018407:Bacterial Physiological Phenomena; D001427:Bacterial Toxins / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D022162:Cytoplasmic Vesicles / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D001427:Bacterial Toxins; D029742:Caenorhabditis elegans Proteins; C558452:Rab-5 protein, C elegans; D033921:Vesicular Transport Proteins; C558453:rab-11.1 protein, C elegans