Rab11A regulates dense granule transport and secretion during Toxoplasma gondii invasion of host cells and parasite replication.
Toxoplasma gondii possesses an armada of secreted virulent factors that enable parasite invasion and survival into host cells. These factors are contained in specific secretory organelles, the rhoptries, micronemes and dense granules that release their content upon host cell recognition. Dense granu...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-05-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1008106 |
| _version_ | 1818587726829584384 |
|---|---|
| author | Kannan Venugopal Sylia Chehade Elisabeth Werkmeister Nicolas Barois Javier Periz Frank Lafont Isabelle Tardieux Jamal Khalife Gordon Langsley Markus Meissner Sabrina Marion |
| author_facet | Kannan Venugopal Sylia Chehade Elisabeth Werkmeister Nicolas Barois Javier Periz Frank Lafont Isabelle Tardieux Jamal Khalife Gordon Langsley Markus Meissner Sabrina Marion |
| author_sort | Kannan Venugopal |
| collection | DOAJ |
| description | Toxoplasma gondii possesses an armada of secreted virulent factors that enable parasite invasion and survival into host cells. These factors are contained in specific secretory organelles, the rhoptries, micronemes and dense granules that release their content upon host cell recognition. Dense granules are secreted in a constitutive manner during parasite replication and play a crucial role in modulating host metabolic and immune responses. While the molecular mechanisms triggering rhoptry and microneme release upon host cell adhesion have been well studied, constitutive secretion remains a poorly explored aspect of T. gondii vesicular trafficking. Here, we investigated the role of the small GTPase Rab11A, a known regulator of exocytosis in eukaryotic cells. Our data revealed an essential role of Rab11A in promoting the cytoskeleton driven transport of dense granules and the release of their content into the vacuolar space. Rab11A also regulates transmembrane protein trafficking and localization during parasite replication, indicating a broader role of Rab11A in cargo exocytosis at the plasma membrane. Moreover, we found that Rab11A also regulates extracellular parasite motility and adhesion to host cells. In line with these findings, MIC2 secretion was altered in Rab11A-defective parasites, which also exhibited severe morphological defects. Strikingly, by live imaging we observed a polarized accumulation of Rab11A-positive vesicles and dense granules at the apical pole of extracellular motile and invading parasites suggesting that apically polarized Rab11A-dependent delivery of cargo regulates early secretory events during parasite entry into host cells. |
| first_indexed | 2024-12-16T09:13:27Z |
| format | Article |
| id | doaj.art-a239896d92e9456983b20a04c3aed2a7 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-16T09:13:27Z |
| publishDate | 2020-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-a239896d92e9456983b20a04c3aed2a72022-12-21T22:36:57ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742020-05-01165e100810610.1371/journal.ppat.1008106Rab11A regulates dense granule transport and secretion during Toxoplasma gondii invasion of host cells and parasite replication.Kannan VenugopalSylia ChehadeElisabeth WerkmeisterNicolas BaroisJavier PerizFrank LafontIsabelle TardieuxJamal KhalifeGordon LangsleyMarkus MeissnerSabrina MarionToxoplasma gondii possesses an armada of secreted virulent factors that enable parasite invasion and survival into host cells. These factors are contained in specific secretory organelles, the rhoptries, micronemes and dense granules that release their content upon host cell recognition. Dense granules are secreted in a constitutive manner during parasite replication and play a crucial role in modulating host metabolic and immune responses. While the molecular mechanisms triggering rhoptry and microneme release upon host cell adhesion have been well studied, constitutive secretion remains a poorly explored aspect of T. gondii vesicular trafficking. Here, we investigated the role of the small GTPase Rab11A, a known regulator of exocytosis in eukaryotic cells. Our data revealed an essential role of Rab11A in promoting the cytoskeleton driven transport of dense granules and the release of their content into the vacuolar space. Rab11A also regulates transmembrane protein trafficking and localization during parasite replication, indicating a broader role of Rab11A in cargo exocytosis at the plasma membrane. Moreover, we found that Rab11A also regulates extracellular parasite motility and adhesion to host cells. In line with these findings, MIC2 secretion was altered in Rab11A-defective parasites, which also exhibited severe morphological defects. Strikingly, by live imaging we observed a polarized accumulation of Rab11A-positive vesicles and dense granules at the apical pole of extracellular motile and invading parasites suggesting that apically polarized Rab11A-dependent delivery of cargo regulates early secretory events during parasite entry into host cells.https://doi.org/10.1371/journal.ppat.1008106 |
| spellingShingle | Kannan Venugopal Sylia Chehade Elisabeth Werkmeister Nicolas Barois Javier Periz Frank Lafont Isabelle Tardieux Jamal Khalife Gordon Langsley Markus Meissner Sabrina Marion Rab11A regulates dense granule transport and secretion during Toxoplasma gondii invasion of host cells and parasite replication. PLoS Pathogens |
| title | Rab11A regulates dense granule transport and secretion during Toxoplasma gondii invasion of host cells and parasite replication. |
| title_full | Rab11A regulates dense granule transport and secretion during Toxoplasma gondii invasion of host cells and parasite replication. |
| title_fullStr | Rab11A regulates dense granule transport and secretion during Toxoplasma gondii invasion of host cells and parasite replication. |
| title_full_unstemmed | Rab11A regulates dense granule transport and secretion during Toxoplasma gondii invasion of host cells and parasite replication. |
| title_short | Rab11A regulates dense granule transport and secretion during Toxoplasma gondii invasion of host cells and parasite replication. |
| title_sort | rab11a regulates dense granule transport and secretion during toxoplasma gondii invasion of host cells and parasite replication |
| url | https://doi.org/10.1371/journal.ppat.1008106 |
| work_keys_str_mv | AT kannanvenugopal rab11aregulatesdensegranuletransportandsecretionduringtoxoplasmagondiiinvasionofhostcellsandparasitereplication AT syliachehade rab11aregulatesdensegranuletransportandsecretionduringtoxoplasmagondiiinvasionofhostcellsandparasitereplication AT elisabethwerkmeister rab11aregulatesdensegranuletransportandsecretionduringtoxoplasmagondiiinvasionofhostcellsandparasitereplication AT nicolasbarois rab11aregulatesdensegranuletransportandsecretionduringtoxoplasmagondiiinvasionofhostcellsandparasitereplication AT javierperiz rab11aregulatesdensegranuletransportandsecretionduringtoxoplasmagondiiinvasionofhostcellsandparasitereplication AT franklafont rab11aregulatesdensegranuletransportandsecretionduringtoxoplasmagondiiinvasionofhostcellsandparasitereplication AT isabelletardieux rab11aregulatesdensegranuletransportandsecretionduringtoxoplasmagondiiinvasionofhostcellsandparasitereplication AT jamalkhalife rab11aregulatesdensegranuletransportandsecretionduringtoxoplasmagondiiinvasionofhostcellsandparasitereplication AT gordonlangsley rab11aregulatesdensegranuletransportandsecretionduringtoxoplasmagondiiinvasionofhostcellsandparasitereplication AT markusmeissner rab11aregulatesdensegranuletransportandsecretionduringtoxoplasmagondiiinvasionofhostcellsandparasitereplication AT sabrinamarion rab11aregulatesdensegranuletransportandsecretionduringtoxoplasmagondiiinvasionofhostcellsandparasitereplication |