Chlamydia-induced curvature of the host-cell plasma membrane is required for infection
| Autor: | Johannes H. Hegemann, Katja Mölleken, Agathe Subtil, Stephan F. Lichtenthaler, Sebastian Hänsch, Gido Murra, Karl Köhrer, Ana Rita Furtado, Bastian Dislich, Dominik Spona |
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| Přispěvatelé: | Functional Genome Research of Microorganisms - Funktionelle Genomforschung der Mikroorganismen [HHU, Dusseldorf], Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Center for Advanced Imaging [HHU, Dusseldorf] (CAI), Biologisch-Medizinisches Forschungszentrum [HHU, Dusseldorf] (BMFZ), Biologie cellulaire de l'Infection microbienne - Cellular Biology of Microbial Infection, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Institute of Pathology, University of Bern, We acknowledge grant support from the Deutsche Forschungsgemeinschaft to J.H.H. (Project-ID 267205415) as part of CRC 1208, and funding of a graduate fellowship by the Jürgen Manchot Foundation., We thank M. A. McNiven for plasmids, Bernd Tebarth for implementing the Chlamydia microarray, Astrid Engel for preparation of protein samples, Elena Görres and David Shi for generating mutant constructs, and the Center of Advnced Imaging for imaging., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Scaffold protein
microbiology [Cell Membrane] genetics [Cell Membrane] Endocytic cycle physiology [Chlamydia] SH3 domain metabolism [Sorting Nexins] membrane modulation [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] lipid binding microbiology [Chlamydia Infections] Chlamydia Internalization Sorting Nexins SNX9 protein human effector protein media_common genetics [Chlamydia Infections] 0303 health sciences Multidisciplinary Chemistry Effector Biological Sciences Endocytosis 3. Good health Cell biology physiopathology [Chlamydia Infections] Host-Pathogen Interactions genetics [Sorting Nexins] ddc:500 genetics [Bacterial Proteins] metabolism [Bacterial Proteins] media_common.quotation_subject 610 Medicine & health Infections chemistry [Cell Membrane] Microbiology metabolism [Cell Membrane] 03 medical and health sciences Bacterial Proteins metabolism [Chlamydia Infections] Humans endocytosis [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM] 030304 developmental biology 030306 microbiology Cell Membrane Chlamydia Infections Sorting nexin Host cell plasma membrane 570 Life sciences biology |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2020, pp.201911528. ⟨10.1073/pnas.1911528117⟩ Proceedings of the National Academy of Sciences of the United States of America 117(5), 2634-2644 (2020). doi:10.1073/pnas.1911528117 Hänsch, Sebastian; Spona, Dominik; Murra, Gido; Köhrer, Karl; Subtil, Agathe; Furtado, Ana Rita; Lichtenthaler, Stephan F; Dislich, Bastian; Mölleken, Katja; Hegemann, Johannes H (2020). Chlamydia-induced curvature of the host-cell plasma membrane is required for infection. Proceedings of the National Academy of Sciences of the United States of America-PNAS, 117(5), pp. 2634-2644. National Academy of Sciences NAS 10.1073/pnas.1911528117 Proceedings of the National Academy of Sciences of the United States of America, 2020, pp.201911528. ⟨10.1073/pnas.1911528117⟩ |
| ISSN: | 0027-8424 1091-6490 |
| DOI: | 10.1073/pnas.1911528117⟩ |
| Popis: | Significance We describe a mechanism by which the obligate intracellular pathogen Chlamydia pneumoniae induces curvature of the host-cell plasma membrane and recruits a central component of the endocytotic machinery. We demonstrate that a type III-secreted C. pneumoniae effector protein named CPn0678 binds via its N-terminal amphipathic helix to negatively charged phospholipids in the inner leaflet of the host plasma membrane at the site of entry, and induces membrane curvature. Its proline-rich region then recruits SNX9 (sorting nexin 9), a key regulator of endocytosis, and the complex facilitates uptake of C. pneumoniae into host cells. During invasion of host cells, Chlamydia pneumoniae secretes the effector protein CPn0678, which facilitates internalization of the pathogen by remodeling the target cell’s plasma membrane and recruiting sorting nexin 9 (SNX9), a central multifunctional endocytic scaffold protein. We show here that the strongly amphipathic N-terminal helix of CPn0678 mediates binding to phospholipids in both the plasma membrane and synthetic membranes, and is sufficient to induce extensive membrane tubulations. CPn0678 interacts via its conserved C-terminal polyproline sequence with the Src homology 3 domain of SNX9. Thus, SNX9 is found at bacterial entry sites, where C. pneumoniae is internalized via EGFR-mediated endocytosis. Moreover, depletion of human SNX9 significantly reduces internalization, whereas ectopic overexpression of CPn0678–GFP results in a dominant-negative effect on endocytotic processes in general, leading to the uptake of fewer chlamydial elementary bodies and diminished turnover of EGFR. Thus, CPn0678 is an early effector involved in regulating the endocytosis of C. pneumoniae in an EGFR- and SNX9-dependent manner. |
| Databáze: | OpenAIRE |
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