{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T21:31:28Z","timestamp":1793223088278,"version":"4.5.0"},"reference-count":50,"publisher":"National Academy of Sciences","issue":"45","license":[{"start":{"date-parts":[[2018,4,23]],"date-time":"2018-04-23T00:00:00Z","timestamp":1524441600000},"content-version":"vor","delay-in-days":182,"URL":"http:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI101441"],"award-info":[{"award-number":["R01AI101441"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32AI007046"],"award-info":[{"award-number":["T32AI007046"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2017,11,7]]},"abstract":"<jats:p>\n                    Membrane contact sites (MCS) are zones of contact between the membranes of two organelles. At MCS, specific proteins tether the organelles in close proximity and mediate the nonvesicular trafficking of lipids and ions between the two organelles. The endoplasmic reticulum (ER) integral membrane protein VAP is a common component of MCS involved in both tethering and lipid transfer by binding directly to proteins containing a FFAT [two phenylalanines (FF) in an acidic tract (AT)] motif. In addition to maintaining cell homeostasis, MCS formation recently emerged as a mechanism by which intracellular pathogens hijack cellular resources and establish their replication niche. Here, we investigated the mechanism by which the\n                    <jats:italic>Chlamydia-<\/jats:italic>\n                    containing vacuole, termed the inclusion, establishes direct contact with the ER. We show that the\n                    <jats:italic>Chlamydia<\/jats:italic>\n                    protein IncV, which is inserted into the inclusion membrane, displays one canonical and one noncanonical FFAT motif that cooperatively mediated the interaction of IncV with VAP. IncV overexpression was sufficient to bring the ER in close proximity of IncV-containing membranes. Although IncV deletion partially decreased VAP association with the inclusion, it did not suppress the formation of ER-inclusion MCS, suggesting the existence of redundant mechanisms in MCS formation. We propose a model in which IncV acts as one of the primary tethers that contribute to the formation of ER-inclusion MCS. Our results highlight a previously unidentified mechanism of bacterial pathogenesis and support the notion that cooperation of two FFAT motifs may be a common feature of VAP-mediated MCS formation.\n                    <jats:italic>Chlamydia<\/jats:italic>\n                    \u2013host cell interaction therefore constitutes a unique system to decipher the molecular mechanisms underlying MCS formation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1709060114","type":"journal-article","created":{"date-parts":[[2017,10,23]],"date-time":"2017-10-23T16:27:30Z","timestamp":1508776050000},"page":"12039-12044","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":106,"title":["IncV, a FFAT motif-containing\n                    <i>Chlamydia<\/i>\n                    protein, tethers the endoplasmic reticulum to the pathogen-containing vacuole"],"prefix":"10.1073","volume":"114","author":[{"given":"Rebecca","family":"Murray","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Flora","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlie","family":"Bayne","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Derr\u00e9","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2017,10,23]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1593"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2013.01.028"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201401126"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2016.10.022"},{"key":"e_1_3_3_5_2","first-page":"5500","article-title":"STARD3 or STARD3NL and VAP form a novel molecular tether between late endosomes and the ER","volume":"126","author":"Alpy F","year":"2013","unstructured":"F Alpy, , STARD3 or STARD3NL and VAP form a novel molecular tether between late endosomes and the ER. 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