{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T19:13:41Z","timestamp":1791832421341,"version":"4.3.4"},"reference-count":49,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,1,31]],"date-time":"2019-01-31T00:00:00Z","timestamp":1548892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI070925"],"award-info":[{"award-number":["AI070925"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000199","name":"U.S. Department of Agriculture","doi-asserted-by":"publisher","award":["PEN04497"],"award-info":[{"award-number":["PEN04497"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>To define the links between paramyxovirus budding and cellular ESCRT machinery, we previously identified angiomotin-like 1 (AMOTL1) in a screen for host factors that bind to the matrix (M) protein of parainfluenza virus 5 (PIV5). This protein harbors three L\/PPXY sequences, allowing it to interact with WW domain containing proteins including NEDD4 family members. We hypothesize that paramyxoviruses use AMOTL1 as a linker to indirectly recruit the same NEDD4 ubiquitin ligases for budding that other enveloped viruses recruit directly through their PPXY late domains. In support of this hypothesis, we found that AMOTL1 could link together M proteins and NEDD4 family proteins in three-way co-IP experiments. Both PIV5 and mumps virus M proteins could be linked to the NEDD4 family proteins NEDD4-1, NEDD4L, and NEDL1, provided that AMOTL1 was co-expressed as a bridging protein. AMOT and AMOTL2 could not substitute for AMOTL1, as they lacked the ability to bind with paramyxovirus M proteins. Attachment of a PPXY late domain sequence to PIV5 M protein obviated the need for AMOTL1 as a linker between M and NEDD4 proteins. Together, these results suggest a novel host factor recruitment strategy for paramyxoviruses to achieve particle release.<\/jats:p>","DOI":"10.3390\/v11020128","type":"journal-article","created":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T03:08:05Z","timestamp":1548990485000},"page":"128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Angiomotin-Like 1 Links Paramyxovirus M Proteins to NEDD4 Family Ubiquitin Ligases"],"prefix":"10.3390","volume":"11","author":[{"given":"Greeshma","family":"Ray","sequence":"first","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phuong Tieu","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9272-058X","authenticated-orcid":false,"given":"Anthony P.","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA"},{"name":"Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,31]]},"reference":[{"key":"ref_1","unstructured":"Knipe, D.M., and Howley, P. (2013). Paramyxoviridae: The viruses and their replication. Fields Virology, Williams and Wilkins. [6th ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.coviro.2017.05.004","article-title":"Structure and organization of paramyxovirus particles","volume":"24","author":"Cox","year":"2017","journal-title":"Curr. Opin. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1016\/j.biocel.2010.04.005","article-title":"Paramyxovirus assembly and budding: Building particles that transmit infections","volume":"42","author":"Harrison","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.chom.2013.08.012","article-title":"Virus budding and the ESCRT pathway","volume":"14","author":"Votteler","year":"2013","journal-title":"Cell Host Microbe"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.coviro.2013.03.011","article-title":"How to get out: ssRNA enveloped viruses and membrane fission","volume":"3","author":"Weissenhorn","year":"2013","journal-title":"Curr. Opin. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.virol.2005.09.044","article-title":"Late budding domains and host proteins in enveloped virus release","volume":"344","author":"Bieniasz","year":"2006","journal-title":"Virology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/S0014-5793(01)03290-2","article-title":"WW and SH3 domains, two different scaffolds to recognize proline-rich ligands","volume":"513","author":"Macias","year":"2002","journal-title":"FEBS Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.devcel.2011.05.015","article-title":"The ESCRT pathway","volume":"21","author":"Henne","year":"2011","journal-title":"Dev. Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3359","DOI":"10.1128\/JVI.73.4.3359-3365.1999","article-title":"Late domain function identified in the vesicular stomatitis virus M protein by use of rhabdovirus-retrovirus chimeras","volume":"73","author":"Craven","year":"1999","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1128\/JVI.73.4.2921-2929.1999","article-title":"A proline-rich motif within the matrix protein of vesicular stomatitis virus and rabies virus interacts with WW domains of cellular proteins: Implications for viral budding","volume":"73","author":"Harty","year":"1999","journal-title":"J. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9818","DOI":"10.1128\/JVI.74.21.9818-9827.2000","article-title":"Mutations in the PPPY motif of vesicular stomatitis virus matrix protein reduce virus budding by inhibiting a late step in virion release","volume":"74","author":"Jayakar","year":"2000","journal-title":"J. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13871","DOI":"10.1073\/pnas.250277297","article-title":"A PPxY motif within the VP40 protein of Ebola virus interacts physically and functionally with a ubiquitin ligase: Implications for filovirus budding","volume":"97","author":"Harty","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1128\/JVI.77.3.1812-1819.2003","article-title":"Overlapping motifs (PTAP and PPEY) within the Ebola virus VP40 protein function independently as late budding domains: Involvement of host proteins TSG101 and VPS-4","volume":"77","author":"Licata","year":"2003","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1038\/nm1201-1313","article-title":"HIV-1 and Ebola virus encode small peptide motifs that recruit Tsg101 to sites of particle assembly to facilitate egress","volume":"7","author":"Zang","year":"2001","journal-title":"Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"12978","DOI":"10.1073\/pnas.2133782100","article-title":"The small RING finger protein Z drives arenavirus budding: Implications for antiviral strategies","volume":"100","author":"Perez","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"9730","DOI":"10.1128\/JVI.00889-08","article-title":"PPEY motif within the rabies virus (RV) matrix protein is essential for efficient virion release and RV pathogenicity","volume":"82","author":"Wirblich","year":"2008","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7261","DOI":"10.1128\/JVI.00421-09","article-title":"Mumps virus matrix, fusion, and nucleocapsid proteins cooperate for efficient production of virus-like particles","volume":"83","author":"Li","year":"2009","journal-title":"J. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2988","DOI":"10.1128\/JVI.79.5.2988-2997.2005","article-title":"Evidence for a new viral late-domain core sequence, FPIV, necessary for budding of a paramyxovirus","volume":"79","author":"Schmitt","year":"2005","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1007\/s00705-014-1998-2","article-title":"Mutations in the FPIV motif of Newcastle disease virus matrix protein attenuate virus replication and reduce virus budding","volume":"159","author":"Duan","year":"2014","journal-title":"Arch. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.virol.2007.09.020","article-title":"Recruitment of Alix\/AIP1 to the plasma membrane by Sendai virus C protein facilitates budding of virus-like particles","volume":"371","author":"Irie","year":"2008","journal-title":"Virology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8933","DOI":"10.1128\/JVI.79.14.8933-8941.2005","article-title":"AIP1\/Alix is a binding partner of Sendai virus C protein and facilitates virus budding","volume":"79","author":"Sakaguchi","year":"2005","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Boonyaratanakornkit, J., Schomacker, H., Collins, P., and Schmidt, A. (2013). Alix serves as an adaptor that allows human parainfluenza virus type 1 to interact with the host cell ESCRT system. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059462"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Park, A., Yun, T., Vigant, F., Pernet, O., Won, S.T., Dawes, B.E., Bartkowski, W., Freiberg, A.N., and Lee, B. (2016). Nipah Virus C Protein Recruits Tsg101 to Promote the Efficient Release of Virus in an ESCRT-Dependent Pathway. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005659"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.virol.2009.11.002","article-title":"PIV5 M protein interaction with host protein angiomotin-like 1","volume":"397","author":"Pei","year":"2010","journal-title":"Virology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2693","DOI":"10.1016\/j.febslet.2014.02.006","article-title":"The Angiomotins--from discovery to function","volume":"588","author":"Moleirinho","year":"2014","journal-title":"FEBS Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"34859","DOI":"10.1074\/jbc.M503915200","article-title":"Angiomotin regulates endothelial cell-cell junctions and cell motility","volume":"280","author":"Bratt","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1161\/CIRCRESAHA.109.195156","article-title":"Angiomotin-like protein 1 controls endothelial polarity and junction stability during sprouting angiogenesis","volume":"105","author":"Zheng","year":"2009","journal-title":"Circ. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5583","DOI":"10.1074\/jbc.M110154200","article-title":"JEAP, a novel component of tight junctions in exocrine cells","volume":"277","author":"Nishimura","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1111\/j.1365-2443.2007.01066.x","article-title":"Molecular characterization of angiomotin\/JEAP family proteins: Interaction with MUPP1\/Patj and their endogenous properties","volume":"12","author":"Adachi","year":"2007","journal-title":"Genes Cells"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.cell.2006.02.045","article-title":"A Rich1\/Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells","volume":"125","author":"Wells","year":"2006","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"ra77","DOI":"10.1126\/scisignal.2004060","article-title":"The p130 isoform of angiomotin is required for Yap-mediated hepatic epithelial cell proliferation and tumorigenesis","volume":"6","author":"Yi","year":"2013","journal-title":"Sci. Signal."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e03778","DOI":"10.7554\/eLife.03778","article-title":"Angiomotin functions in HIV-1 assembly and budding","volume":"4","author":"Mercenne","year":"2015","journal-title":"eLife"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4884","DOI":"10.1128\/JVI.02667-07","article-title":"NEDD4L overexpression rescues the release and infectivity of human immunodeficiency virus type 1 constructs lacking PTAP and YPXL late domains","volume":"82","author":"Chung","year":"2008","journal-title":"J. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4898","DOI":"10.1128\/JVI.02675-07","article-title":"Efficient and specific rescue of human immunodeficiency virus type 1 budding defects by a Nedd4-like ubiquitin ligase","volume":"82","author":"Usami","year":"2008","journal-title":"J. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3952","DOI":"10.1128\/JVI.76.8.3952-3964.2002","article-title":"Requirements for budding of paramyxovirus simian virus 5 virus-like particles","volume":"76","author":"Schmitt","year":"2002","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0378-1119(91)90434-D","article-title":"Efficient selection for high-expression transfectants with a novel eukaryotic vector","volume":"108","author":"Niwa","year":"1991","journal-title":"Gene"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1093\/bioinformatics\/btm404","article-title":"Clustal W and Clustal X version 2.0","volume":"23","author":"Larkin","year":"2007","journal-title":"Bioinformatics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1099\/0022-1317-68-11-2769","article-title":"Isolation and characterization of monoclonal antibodies to simian virus 5 and their use in revealing antigenic differences between human, canine and simian isolates","volume":"68","author":"Randall","year":"1987","journal-title":"J. Gen. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"12810","DOI":"10.1128\/JVI.01885-10","article-title":"The C-terminal end of parainfluenza virus 5 NP protein is important for virus-like particle production and M-NP protein interaction","volume":"84","author":"Schmitt","year":"2010","journal-title":"J. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Skouloudaki, K., and Walz, G. (2012). YAP1 recruits c-Abl to protect angiomotin-like 1 from Nedd4-mediated degradation. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035735"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1016\/j.cellsig.2016.07.015","article-title":"The endothelial E3 ligase HECW2 promotes endothelial cell junctions by increasing AMOTL1 protein stability via K63-linked ubiquitination","volume":"28","author":"Choi","year":"2016","journal-title":"Cell Signal."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.antiviral.2008.12.003","article-title":"No exit: Targeting the budding process to inhibit filovirus replication","volume":"81","author":"Harty","year":"2009","journal-title":"Antivir. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"528","DOI":"10.3390\/v5020528","article-title":"Arenavirus budding: A common pathway with mechanistic differences","volume":"5","author":"Wolff","year":"2013","journal-title":"Viruses"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1111\/j.1600-0854.2011.01242.x","article-title":"How ubiquitin functions with ESCRTs","volume":"12","author":"Shields","year":"2011","journal-title":"Traffic"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0092-8674(01)00506-2","article-title":"Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding","volume":"107","author":"Garrus","year":"2001","journal-title":"Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3474","DOI":"10.1128\/JVI.06021-11","article-title":"Role of ubiquitin in parainfluenza virus 5 particle formation","volume":"86","author":"Harrison","year":"2012","journal-title":"J. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Pentecost, M., Vashisht, A.A., Lester, T., Voros, T., Beaty, S.M., Park, A., Wang, Y.E., Yun, T.E., Freiberg, A.N., and Wohlschlegel, J.A. (2015). Evidence for ubiquitin-regulated nuclear and subnuclear trafficking among Paramyxovirinae matrix proteins. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004739"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Wang, Y.E., Park, A., Lake, M., Pentecost, M., Torres, B., Yun, T.E., Wolf, M.C., Holbrook, M.R., Freiberg, A.N., and Lee, B. (2010). Ubiquitin-regulated nuclear-cytoplasmic trafficking of the Nipah virus matrix protein is important for viral budding. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1001186"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1091\/mbc.e13-11-0701","article-title":"Angiomotins link F-actin architecture to Hippo pathway signaling","volume":"25","author":"Paramasivam","year":"2014","journal-title":"Mol. Biol. Cell"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/11\/2\/128\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:29:53Z","timestamp":1760185793000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/11\/2\/128"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,31]]},"references-count":49,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,2]]}},"alternative-id":["v11020128"],"URL":"https:\/\/doi.org\/10.3390\/v11020128","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,31]]}}}