Host endoplasmic reticulum COPII proteins control cell-to-cell spread of the bacterial pathogenListeria monocytogenes

Autor: Tina McDivitt, Nilakshee Bhattacharya, Luciano A. Rigano, Wanjin Hong, Antonella Gianfelice, Phuong H.B. Le, Georgina C. Dowd, Susan Saila, Keith Ireton, Scott M. Stagg
Rok vydání: 2015
Předmět:
Zdroj: Cellular Microbiology. 17:876-892
ISSN: 1462-5814
DOI: 10.1111/cmi.12409
Popis: Summary Listeria monocytogenes is a food-borne pathogen that uses actin-dependent motility to spread between human cells. Cell-to-cell spread involves the formation by motile bacteria of plasma membrane-derived structures termed 'protru- sions'. In cultured enterocytes, the secreted Listeria protein InlC promotes protrusion forma- tion by binding and inhibiting the human scaffold- ing protein Tuba. Here we demonstrate that protrusions are controlled by human COPII com- ponents that direct trafficking from the endo- plasmic reticulum. Co-precipitation experiments indicated that the COPII proteins Sec31A and Sec13 interact directly with a Src homology 3 domain in Tuba. This interaction was antagonized by InlC. Depletion of Sec31A or Sec13 restored normal protrusion formation to a Listeria mutant lacking inlC, without affecting spread of wild-type bacteria. Genetic impairment of the COPII compo- nent Sar1 or treatment of cells with brefeldin A affected protrusions similarly to Sec31A or Sec13 depletion. These findings indicated that InlC relieves a host-mediated restriction of Listeria spread otherwise imposed by COPII. Inhibition of Sec31A, Sec13 or Sar1 or brefeldin A treatment also perturbed the structure of cell-cell junctions. Collectively, these findings demonstrate an impor- tant role for COPII in controlling Listeria spread. We propose that COPII may act by delivering host proteins that generate tension at cell junctions.
Databáze: OpenAIRE
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