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

Kyle Caution; Mikhail A Gavrilin; Mia Tazi; Apurva Kanneganti; Daniel Layman; Sheshadri Hoque; Kathrin Krause; Amal O Amer

doi:10.1038/srep18479

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.

Authors

Kyle Caution^{1

2}, Mikhail A Gavrilin², Mia Tazi^{1

2}, Apurva Kanneganti^{1

2}, Daniel Layman^{1

2}, Sheshadri Hoque^{1

2}, Kathrin Krause^{1

2}, Amal O Amer^{1

2}

Affiliations

¹ Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, Columbus OH 43210.
² Dorothy M. Davis Heart and Lung Research Institute, and The Ohio State University, Columbus OH 43210.

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

Abstract

Publication types

MeSH terms

Substances

Grants and funding