Epithelial Keratins Modulate cMet Expression and Signaling and Promote InlB-Mediated Listeria monocytogenes Infection of HeLa Cells
The host cytoskeleton is a major target for bacterial pathogens during infection. In particular, pathogens usurp the actin cytoskeleton function to strongly adhere to the host cell surface, to induce plasma membrane remodeling allowing invasion and to spread from cell to cell and disseminate to the...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-05-01
|
| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fcimb.2018.00146/full |
| _version_ | 1819073936556556288 |
|---|---|
| author | Rui Cruz Rui Cruz Rui Cruz Isabel Pereira-Castro Isabel Pereira-Castro Maria T. Almeida Maria T. Almeida Alexandra Moreira Alexandra Moreira Alexandra Moreira Didier Cabanes Didier Cabanes Sandra Sousa Sandra Sousa |
| author_facet | Rui Cruz Rui Cruz Rui Cruz Isabel Pereira-Castro Isabel Pereira-Castro Maria T. Almeida Maria T. Almeida Alexandra Moreira Alexandra Moreira Alexandra Moreira Didier Cabanes Didier Cabanes Sandra Sousa Sandra Sousa |
| author_sort | Rui Cruz |
| collection | DOAJ |
| description | The host cytoskeleton is a major target for bacterial pathogens during infection. In particular, pathogens usurp the actin cytoskeleton function to strongly adhere to the host cell surface, to induce plasma membrane remodeling allowing invasion and to spread from cell to cell and disseminate to the whole organism. Keratins are cytoskeletal proteins that are the major components of intermediate filaments in epithelial cells however, their role in bacterial infection has been disregarded. Here we investigate the role of the major epithelial keratins, keratins 8 and 18 (K8 and K18), in the cellular infection by Listeria monocytogenes. We found that K8 and K18 are required for successful InlB/cMet-dependent L. monocytogenes infection, but are dispensable for InlA/E-cadherin-mediated invasion. Both K8 and K18 accumulate at InlB-mediated internalization sites following actin recruitment and modulate actin dynamics at those sites. We also reveal the key role of K8 and K18 in HGF-induced signaling which occurs downstream the activation of cMet. Strikingly, we show here that K18, and at a less extent K8, controls the expression of cMet and other surface receptors such TfR and integrin β1, by promoting the stability of their corresponding transcripts. Together, our results reveal novel functions for major epithelial keratins in the modulation of actin dynamics at the bacterial entry sites and in the control of surface receptors mRNA stability and expression. |
| first_indexed | 2024-12-21T18:01:32Z |
| format | Article |
| id | doaj.art-ba22c5bc0de046008888eec0740ea7dd |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-21T18:01:32Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-ba22c5bc0de046008888eec0740ea7dd2022-12-21T18:55:03ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882018-05-01810.3389/fcimb.2018.00146336236Epithelial Keratins Modulate cMet Expression and Signaling and Promote InlB-Mediated Listeria monocytogenes Infection of HeLa CellsRui Cruz0Rui Cruz1Rui Cruz2Isabel Pereira-Castro3Isabel Pereira-Castro4Maria T. Almeida5Maria T. Almeida6Alexandra Moreira7Alexandra Moreira8Alexandra Moreira9Didier Cabanes10Didier Cabanes11Sandra Sousa12Sandra Sousa13Group of Molecular Microbiology, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, PortugalGroup of Molecular Microbiology, Institute for Molecular and Cell Biology, Porto, PortugalInstituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, PortugalGroup of Molecular Microbiology, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, PortugalGene Regulation Group, Institute for Molecular and Cell Biology, Porto, PortugalGroup of Molecular Microbiology, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, PortugalGroup of Molecular Microbiology, Institute for Molecular and Cell Biology, Porto, PortugalGroup of Molecular Microbiology, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, PortugalInstituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, PortugalGene Regulation Group, Institute for Molecular and Cell Biology, Porto, PortugalGroup of Molecular Microbiology, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, PortugalGroup of Molecular Microbiology, Institute for Molecular and Cell Biology, Porto, PortugalGroup of Molecular Microbiology, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, PortugalGroup of Molecular Microbiology, Institute for Molecular and Cell Biology, Porto, PortugalThe host cytoskeleton is a major target for bacterial pathogens during infection. In particular, pathogens usurp the actin cytoskeleton function to strongly adhere to the host cell surface, to induce plasma membrane remodeling allowing invasion and to spread from cell to cell and disseminate to the whole organism. Keratins are cytoskeletal proteins that are the major components of intermediate filaments in epithelial cells however, their role in bacterial infection has been disregarded. Here we investigate the role of the major epithelial keratins, keratins 8 and 18 (K8 and K18), in the cellular infection by Listeria monocytogenes. We found that K8 and K18 are required for successful InlB/cMet-dependent L. monocytogenes infection, but are dispensable for InlA/E-cadherin-mediated invasion. Both K8 and K18 accumulate at InlB-mediated internalization sites following actin recruitment and modulate actin dynamics at those sites. We also reveal the key role of K8 and K18 in HGF-induced signaling which occurs downstream the activation of cMet. Strikingly, we show here that K18, and at a less extent K8, controls the expression of cMet and other surface receptors such TfR and integrin β1, by promoting the stability of their corresponding transcripts. Together, our results reveal novel functions for major epithelial keratins in the modulation of actin dynamics at the bacterial entry sites and in the control of surface receptors mRNA stability and expression.http://journal.frontiersin.org/article/10.3389/fcimb.2018.00146/fullintermediate filamentskeratinscMet signalingListeria monocytogenescellular infectionmRNA stability |
| spellingShingle | Rui Cruz Rui Cruz Rui Cruz Isabel Pereira-Castro Isabel Pereira-Castro Maria T. Almeida Maria T. Almeida Alexandra Moreira Alexandra Moreira Alexandra Moreira Didier Cabanes Didier Cabanes Sandra Sousa Sandra Sousa Epithelial Keratins Modulate cMet Expression and Signaling and Promote InlB-Mediated Listeria monocytogenes Infection of HeLa Cells Frontiers in Cellular and Infection Microbiology intermediate filaments keratins cMet signaling Listeria monocytogenes cellular infection mRNA stability |
| title | Epithelial Keratins Modulate cMet Expression and Signaling and Promote InlB-Mediated Listeria monocytogenes Infection of HeLa Cells |
| title_full | Epithelial Keratins Modulate cMet Expression and Signaling and Promote InlB-Mediated Listeria monocytogenes Infection of HeLa Cells |
| title_fullStr | Epithelial Keratins Modulate cMet Expression and Signaling and Promote InlB-Mediated Listeria monocytogenes Infection of HeLa Cells |
| title_full_unstemmed | Epithelial Keratins Modulate cMet Expression and Signaling and Promote InlB-Mediated Listeria monocytogenes Infection of HeLa Cells |
| title_short | Epithelial Keratins Modulate cMet Expression and Signaling and Promote InlB-Mediated Listeria monocytogenes Infection of HeLa Cells |
| title_sort | epithelial keratins modulate cmet expression and signaling and promote inlb mediated listeria monocytogenes infection of hela cells |
| topic | intermediate filaments keratins cMet signaling Listeria monocytogenes cellular infection mRNA stability |
| url | http://journal.frontiersin.org/article/10.3389/fcimb.2018.00146/full |
| work_keys_str_mv | AT ruicruz epithelialkeratinsmodulatecmetexpressionandsignalingandpromoteinlbmediatedlisteriamonocytogenesinfectionofhelacells AT ruicruz epithelialkeratinsmodulatecmetexpressionandsignalingandpromoteinlbmediatedlisteriamonocytogenesinfectionofhelacells AT ruicruz epithelialkeratinsmodulatecmetexpressionandsignalingandpromoteinlbmediatedlisteriamonocytogenesinfectionofhelacells AT isabelpereiracastro epithelialkeratinsmodulatecmetexpressionandsignalingandpromoteinlbmediatedlisteriamonocytogenesinfectionofhelacells AT isabelpereiracastro epithelialkeratinsmodulatecmetexpressionandsignalingandpromoteinlbmediatedlisteriamonocytogenesinfectionofhelacells AT mariatalmeida epithelialkeratinsmodulatecmetexpressionandsignalingandpromoteinlbmediatedlisteriamonocytogenesinfectionofhelacells AT mariatalmeida epithelialkeratinsmodulatecmetexpressionandsignalingandpromoteinlbmediatedlisteriamonocytogenesinfectionofhelacells AT alexandramoreira epithelialkeratinsmodulatecmetexpressionandsignalingandpromoteinlbmediatedlisteriamonocytogenesinfectionofhelacells AT alexandramoreira epithelialkeratinsmodulatecmetexpressionandsignalingandpromoteinlbmediatedlisteriamonocytogenesinfectionofhelacells AT alexandramoreira epithelialkeratinsmodulatecmetexpressionandsignalingandpromoteinlbmediatedlisteriamonocytogenesinfectionofhelacells AT didiercabanes epithelialkeratinsmodulatecmetexpressionandsignalingandpromoteinlbmediatedlisteriamonocytogenesinfectionofhelacells AT didiercabanes epithelialkeratinsmodulatecmetexpressionandsignalingandpromoteinlbmediatedlisteriamonocytogenesinfectionofhelacells AT sandrasousa epithelialkeratinsmodulatecmetexpressionandsignalingandpromoteinlbmediatedlisteriamonocytogenesinfectionofhelacells AT sandrasousa epithelialkeratinsmodulatecmetexpressionandsignalingandpromoteinlbmediatedlisteriamonocytogenesinfectionofhelacells |