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To create its replicative niche,\n                    <jats:italic>L<\/jats:italic>\n                    .\n                    <jats:italic>pneumophila<\/jats:italic>\n                    manipulates host membrane traffic and fusion machineries. Bacterial proteins called\n                    <jats:italic>Legionella<\/jats:italic>\n                    effectors are translocated into the host cytosol and play a crucial role in these processes. In an early stage of infection,\n                    <jats:italic>Legionella<\/jats:italic>\n                    subverts ER-derived vesicles (ERDVs) by manipulating GTPase Rab1 to facilitate remodeling of the\n                    <jats:italic>Legionella<\/jats:italic>\n                    -containing vacuole (LCV). Subsequently, the LCV associates with the ER in a mechanism that remains elusive. In this study, we show that\n                    <jats:italic>L<\/jats:italic>\n                    .\n                    <jats:italic>pneumophila<\/jats:italic>\n                    recruits GTPases Rab33B and Rab6A, which regulate vesicle trafficking from the Golgi to the ER, to the LCV to promote the association of LCV with the ER. We found that recruitment of Rab6A to the LCV depends on Rab33B.\n                    <jats:italic>Legionella<\/jats:italic>\n                    effector SidE family proteins, which phosphoribosyl-ubiquitinate Rab33B, were found to be necessary for the recruitment of Rab33B to the LCV. Immunoprecipitation experiments revealed that\n                    <jats:italic>L<\/jats:italic>\n                    .\n                    <jats:italic>pneumophila<\/jats:italic>\n                    facilitates the interaction of Rab6 with ER-resident SNAREs comprising syntaxin 18, p31, and BNIP1, but not tethering factors including NAG, RINT-1, and ZW10, which are normally required for syntaxin 18-mediated fusion of Golgi-derived vesicles with the ER. Our results identified a Rab33B-Rab6A cascade on the LCV and the interaction of Rab6 with ER-resident SNARE proteins for the association of LCV with the ER and disclosed the unidentified physiological role of SidE family proteins.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009437","type":"journal-article","created":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T13:44:56Z","timestamp":1616593496000},"page":"e1009437","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":47,"title":["Legionella hijacks the host Golgi-to-ER retrograde pathway for the association of Legionella-containing vacuole with the ER"],"prefix":"10.1371","volume":"17","author":[{"given":"Mio","family":"Kawabata","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honoka","family":"Matsuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Koito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misaki","family":"Murata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Kubori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1659-2197","authenticated-orcid":true,"given":"Hiroki","family":"Nagai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9137-7142","authenticated-orcid":true,"given":"Mitsuo","family":"Tagaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0647-3565","authenticated-orcid":true,"given":"Kohei","family":"Arasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,3,24]]},"reference":[{"key":"ppat.1009437.ref001","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1146\/annurev-cellbio-100109-104034","article-title":"Modulation of host cell function by Legionella pneumophila type IV effectors","volume":"26","author":"A Hubber","year":"2010","journal-title":"Annu. 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