Salmonella exploits LRRK2-dependent plasma membrane dynamics to invade host cells
Abstract Salmonella utilizes type 3 secreted effector proteins to induce plasma membrane (PM) perturbations during invasion of host cells1. The effectors drive mobilization of host membranes to generate cell surface ruffles, followed by invagination and scission of the PM to generate Salmonella-cont...
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Nature Portfolio
2025-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-57453-x |
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| _version_ | 1850027931215069184 |
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| author | Hongxian Zhu Andrew M. Sydor Bing-Ru Yan Ren Li Michal T. Boniecki Carina Lyons Miroslaw Cygler Aleixo M. Muise Michelle E. Maxson Sergio Grinstein Brian Raught John H. Brumell |
| author_facet | Hongxian Zhu Andrew M. Sydor Bing-Ru Yan Ren Li Michal T. Boniecki Carina Lyons Miroslaw Cygler Aleixo M. Muise Michelle E. Maxson Sergio Grinstein Brian Raught John H. Brumell |
| author_sort | Hongxian Zhu |
| collection | DOAJ |
| description | Abstract Salmonella utilizes type 3 secreted effector proteins to induce plasma membrane (PM) perturbations during invasion of host cells1. The effectors drive mobilization of host membranes to generate cell surface ruffles, followed by invagination and scission of the PM to generate Salmonella-containing vacuoles (SCVs)2. Here, we show that LRRK2 kinase generates membrane reservoirs exploited by Salmonella during invasion. The reservoirs are tubular compartments associated with the PM under basal conditions and are formed through the phosphorylation of RAB10 GTPase by LRRK2. Mobilization of membrane reservoirs to generate invasion ruffles mediates delivery of phosphorylated RAB10 to invasion sites. Subsequently, RAB10 dephosphorylation is required for its inactivation by a bacterial GTPase activating protein and subsequent scission of the PM. RAB10 dephosphorylation is mediated by a TLR4/PIEZO1/TMEM16F-dependent pathway and is inhibited by hyperactive variants of LRRK2. Our findings reveal how Salmonella exploits LRRK2-dependent PM dynamics during invasion and provide new insight into how LRRK2 variants can protect against bacterial infection3,4. |
| format | Article |
| id | doaj-art-057364dc9d0b44979da0ca2cc68c0a2d |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-057364dc9d0b44979da0ca2cc68c0a2d2025-08-20T02:59:58ZengNature PortfolioNature Communications2041-17232025-03-0116111810.1038/s41467-025-57453-xSalmonella exploits LRRK2-dependent plasma membrane dynamics to invade host cellsHongxian Zhu0Andrew M. Sydor1Bing-Ru Yan2Ren Li3Michal T. Boniecki4Carina Lyons5Miroslaw Cygler6Aleixo M. Muise7Michelle E. Maxson8Sergio Grinstein9Brian Raught10John H. Brumell11Cell Biology Program, Hospital for Sick ChildrenCell Biology Program, Hospital for Sick ChildrenCell Biology Program, Hospital for Sick ChildrenCell Biology Program, Hospital for Sick ChildrenDepartment of Biochemistry, Microbiology and Immunology, University of SaskatchewanCell Biology Program, Hospital for Sick ChildrenDepartment of Biochemistry, Microbiology and Immunology, University of SaskatchewanCell Biology Program, Hospital for Sick ChildrenCell Biology Program, Hospital for Sick ChildrenCell Biology Program, Hospital for Sick ChildrenPrincess Margaret Cancer Centre, University Health NetworkCell Biology Program, Hospital for Sick ChildrenAbstract Salmonella utilizes type 3 secreted effector proteins to induce plasma membrane (PM) perturbations during invasion of host cells1. The effectors drive mobilization of host membranes to generate cell surface ruffles, followed by invagination and scission of the PM to generate Salmonella-containing vacuoles (SCVs)2. Here, we show that LRRK2 kinase generates membrane reservoirs exploited by Salmonella during invasion. The reservoirs are tubular compartments associated with the PM under basal conditions and are formed through the phosphorylation of RAB10 GTPase by LRRK2. Mobilization of membrane reservoirs to generate invasion ruffles mediates delivery of phosphorylated RAB10 to invasion sites. Subsequently, RAB10 dephosphorylation is required for its inactivation by a bacterial GTPase activating protein and subsequent scission of the PM. RAB10 dephosphorylation is mediated by a TLR4/PIEZO1/TMEM16F-dependent pathway and is inhibited by hyperactive variants of LRRK2. Our findings reveal how Salmonella exploits LRRK2-dependent PM dynamics during invasion and provide new insight into how LRRK2 variants can protect against bacterial infection3,4.https://doi.org/10.1038/s41467-025-57453-x |
| spellingShingle | Hongxian Zhu Andrew M. Sydor Bing-Ru Yan Ren Li Michal T. Boniecki Carina Lyons Miroslaw Cygler Aleixo M. Muise Michelle E. Maxson Sergio Grinstein Brian Raught John H. Brumell Salmonella exploits LRRK2-dependent plasma membrane dynamics to invade host cells Nature Communications |
| title | Salmonella exploits LRRK2-dependent plasma membrane dynamics to invade host cells |
| title_full | Salmonella exploits LRRK2-dependent plasma membrane dynamics to invade host cells |
| title_fullStr | Salmonella exploits LRRK2-dependent plasma membrane dynamics to invade host cells |
| title_full_unstemmed | Salmonella exploits LRRK2-dependent plasma membrane dynamics to invade host cells |
| title_short | Salmonella exploits LRRK2-dependent plasma membrane dynamics to invade host cells |
| title_sort | salmonella exploits lrrk2 dependent plasma membrane dynamics to invade host cells |
| url | https://doi.org/10.1038/s41467-025-57453-x |
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