Aaron S Dhanda1, Katarina T Lulic1, A Wayne Vogl2, Margaret M Mc Gee3, Robert H Chiu4,5, Julian A Guttman1. 1. Department of Biological Sciences, Centre for Cell Biology, Development, and Disease, Simon Fraser University, Burnaby, British Columbia, Canada. 2. Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, Vancouver, Canada. 3. School of Biomolecular and Biomedical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Ireland. 4. Dental and Craniofacial Research Institute and School of Dentistry, University of California, Los Angeles. 5. Surgical Oncology and Jonsson Comprehensive Cancer Center, University of California, Los Angeles.
Abstract
Background: Listeria generate actin-rich tubular protrusions at the plasma membrane that propel the bacteria into neighboring cells. The precise molecular mechanisms governing the formation of these protrusions remain poorly defined. Methods: In this study, we demonstrate that the prolyl cis-trans isomerase (PPIase) cyclophilin A (CypA) is hijacked by Listeria at membrane protrusions used for cell-to-cell spreading. Results: Cyclophilin A localizes within the F-actin of these structures and is crucial for their proper formation, as cells depleted of CypA have extended actin-rich structures that are misshaped and are collapsed due to changes within the F-actin network. The lack of structural integrity within the Listeria membrane protrusions hampers the microbes from spreading from CypA null cells. Conclusions: Our results demonstrate a crucial role for CypA during Listeria infections.
Background: Listeria generate actin-rich tubular protrusions at the plasma membrane that propel the bacteria into neighboring cells. The precise molecular mechanisms governing the formation of these protrusions remain poorly defined. Methods: In this study, we demonstrate that the prolyl cis-trans isomerase (PPIase) cyclophilin A (CypA) is hijacked by Listeria at membrane protrusions used for cell-to-cell spreading. Results:Cyclophilin A localizes within the F-actin of these structures and is crucial for their proper formation, as cells depleted of CypA have extended actin-rich structures that are misshaped and are collapsed due to changes within the F-actin network. The lack of structural integrity within the Listeria membrane protrusions hampers the microbes from spreading from CypA null cells. Conclusions: Our results demonstrate a crucial role for CypA during Listeria infections.
Authors: Aaron S Dhanda; Katarina T Lulic; Connie Yu; Robert H Chiu; Michael Bukrinsky; Julian A Guttman Journal: Cell Mol Life Sci Date: 2019-05-10 Impact factor: 9.261
Authors: Aaron S Dhanda; Connie Yu; Katarina T Lulic; A Wayne Vogl; Valentina Rausch; Diana Yang; Benjamin J Nichols; Sung Hyun Kim; Simona Polo; Carsten G Hansen; Julian A Guttman Journal: mBio Date: 2020-01-21 Impact factor: 7.867