{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:59:35Z","timestamp":1791331175049,"version":"4.3.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010433","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T00:00:00Z","timestamp":1649203200000}}],"reference-count":67,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T00:00:00Z","timestamp":1648166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DGE-1762114"],"award-info":[{"award-number":["DGE-1762114"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F31HL156697"],"award-info":[{"award-number":["F31HL156697"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["S10 OD021490"],"award-info":[{"award-number":["S10 OD021490"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    The deep-branching eukaryote\n                    <jats:italic>Giardia lamblia<\/jats:italic>\n                    is an extracellular parasite that attaches to the host intestine via a microtubule-based structure called the ventral disc. Control of attachment is mediated in part by the movement of two regions of the ventral disc that either permit or exclude the passage of fluid under the disc. Several known disc-associated proteins (DAPs) contribute to disc structure and function, but no force-generating protein has been identified among them. We recently identified several\n                    <jats:italic>Giardia<\/jats:italic>\n                    actin (\n                    <jats:italic>Gl<\/jats:italic>\n                    Actin) interacting proteins at the ventral disc, which could potentially employ actin polymerization for force generation and disc conformational changes. One of these proteins, Disc and Actin Associated Protein 1 (DAAP1), is highly enriched at the two regions of the disc previously shown to be important for fluid flow during attachment. In this study, we investigate the role of both\n                    <jats:italic>Gl<\/jats:italic>\n                    Actin and DAAP1 in ventral disc morphology and function. We confirmed interaction between\n                    <jats:italic>Gl<\/jats:italic>\n                    Actin and DAAP1 through coimmunoprecipitation, and used immunofluorescence to localize both proteins throughout the cell cycle and during trophozoite attachment. Similar to other DAPs, the association of DAAP1 with the disc is stable, except during cell division when the disc disassembles. Depletion of\n                    <jats:italic>Gl<\/jats:italic>\n                    Actin by translation-blocking antisense morpholinos resulted in both impaired attachment and defects in the ventral disc, indicating that\n                    <jats:italic>Gl<\/jats:italic>\n                    Actin contributes to disc-mediated attachment. Depletion of DAAP1 through CRISPR interference resulted in intact discs but impaired attachment, gating, and flow under the disc. As attachment is essential for infection, elucidation of these and other molecular mediators is a promising area for development of new therapeutics against a ubiquitous parasite.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1010433","type":"journal-article","created":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T13:48:50Z","timestamp":1648216130000},"page":"e1010433","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Disc and Actin Associated Protein 1 influences attachment in the intestinal parasite Giardia lamblia"],"prefix":"10.1371","volume":"18","author":[{"given":"Melissa C.","family":"Steele-Ogus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ava M.","family":"Obenaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan J.","family":"Sniadecki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9298-3264","authenticated-orcid":true,"given":"Alexander R.","family":"Paredez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,3,25]]},"reference":[{"key":"ppat.1010433.ref001","doi-asserted-by":"crossref","DOI":"10.1080\/1040-840291046713","article-title":"Current Trends in Research into the Waterborne Parasite Giardia","volume":"28","author":"S Lane","year":"2002","journal-title":"Critical Reviews in Microbiology"},{"key":"ppat.1010433.ref002","doi-asserted-by":"crossref","DOI":"10.1016\/j.pt.2006.02.015","article-title":"Giardia and Cryptosporidium join the \u2018Neglected Diseases Initiative.\u2019","volume":"22","author":"L Savioli","year":"2006","journal-title":"Trends in 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Elmendorf","year":"2003","journal-title":"International Journal for Parasitology"},{"key":"ppat.1010433.ref007","doi-asserted-by":"crossref","DOI":"10.1007\/s40588-015-0026-y","article-title":"The Critical Role of the Cytoskeleton in the Pathogenesis of Giardia.","volume":"2","author":"C Nosala","year":"2015","journal-title":"Current Clinical Microbiology Reports"},{"key":"ppat.1010433.ref008","article-title":"The ventral disc is a flexible microtubule organelle that depends on domed ultrastructure for functional attachment of Giardia lamblia","author":"C Nosala","year":"2017","journal-title":"bioRxiv. bioRxiv"},{"key":"ppat.1010433.ref009","doi-asserted-by":"crossref","DOI":"10.1016\/j.tcb.2017.10.007","article-title":"\u2018Disc-o-Fever\u2019: Getting Down with Giardia\u2019s Groovy Microtubule Organelle","volume":"28","author":"C Nosala","year":"2018","journal-title":"Trends in Cell 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Palm","year":"2005","journal-title":"Molecular and Biochemical Parasitology"},{"key":"ppat.1010433.ref058","article-title":"Cas9-mediated gene disruption in tetraploid Giardia intestinalis.","author":"V Hor\u00e1\u010dkov\u00e1","year":"2021","journal-title":"Biorxiv"},{"key":"ppat.1010433.ref059","article-title":"Role of gamma-giardin in ventral disc formation of Giardia lamblia.","volume":"12","author":"J Kim","year":"2019","journal-title":"Parasites & Vectors"},{"key":"ppat.1010433.ref060","article-title":"The Giardia lamellipodium-like ventrolateral flange supports attachment and rapid cytokinesis","author":"WR Hardin","year":"2021","journal-title":"Biorxiv"},{"key":"ppat.1010433.ref061","doi-asserted-by":"crossref","DOI":"10.1111\/j.1550-7408.2004.tb00165.x","article-title":",Evidence for Adhesive Activity of the Ventrolateral Flange in Giardia lamblia","volume":"51","author":"SL ERLANDSEN","year":"2004","journal-title":"The Journal of Eukaryotic 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