Caspase-11 and caspase-1 differentially modulate actin polymerization via RhoA and Slingshot proteins to promote bacterial clearance

Sci Rep. 2015 Dec 21;5:18479. doi: 10.1038/srep18479.

Abstract

Inflammasomes are multiprotein complexes that include members of the NOD-like receptor family and caspase-1. Caspase-1 is required for the fusion of the Legionella vacuole with lysosomes. Caspase-11, independently of the inflammasome, also promotes phagolysosomal fusion. However, it is unclear how these proteases alter intracellular trafficking. Here, we show that caspase-11 and caspase-1 function in opposing manners to phosphorylate and dephosphorylate cofilin, respectively upon infection with Legionella. Caspase-11 targets cofilin via the RhoA GTPase, whereas caspase-1 engages the Slingshot phosphatase. The absence of either caspase-11 or caspase-1 maintains actin in the polymerized or depolymerized form, respectively and averts the fusion of pathogen-containing vacuoles with lysosomes. Therefore, caspase-11 and caspase-1 converge on the actin machinery with opposing effects to promote vesicular trafficking.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Actins / metabolism*
  • Animals
  • Caspase 1 / genetics*
  • Caspase 1 / metabolism
  • Cofilin 1 / genetics*
  • Cofilin 1 / metabolism
  • Humans
  • Inflammasomes / genetics
  • Inflammasomes / metabolism
  • Legionella pneumophila / genetics
  • Legionella pneumophila / pathogenicity
  • Legionnaires' Disease / genetics*
  • Legionnaires' Disease / metabolism
  • Legionnaires' Disease / pathology
  • Lysosomes / genetics
  • Lysosomes / metabolism
  • Mice
  • Mice, Knockout
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / metabolism*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Vacuoles / genetics
  • Vacuoles / metabolism
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism
  • rhoA GTP-Binding Protein / genetics
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • Actins
  • Cofilin 1
  • Inflammasomes
  • Multiprotein Complexes
  • Receptors, Cell Surface
  • Vesicular Transport Proteins
  • Phosphoprotein Phosphatases
  • SSH1 protein, mouse
  • Caspase 1
  • rhoA GTP-Binding Protein