{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T21:23:49Z","timestamp":1792185829738,"version":"4.4.0"},"reference-count":82,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2009,12,27]],"date-time":"2009-12-27T00:00:00Z","timestamp":1261872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI068033"],"award-info":[{"award-number":["AI068033"]}],"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":["AI081972"],"award-info":[{"award-number":["AI081972"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>CD46 is a type I transmembrane protein with complement and T cell regulatory functions in human cells. CD46 has signaling and receptor properties in immune and nonimmune cells, many of which are dependent on the expression of cytoplasmic tail (cyt) isoforms cyt1 or cyt2. Little is known about how cyt1 and cyt2 mediate cellular responses. We show that CD46-cyt1 and CD46-cyt2 are substrates for presenilin\/\u03b3-secretase (PS\/\u03b3S), an endogenous protease complex that regulates many important signaling proteins through proteolytic processing. PS\/\u03b3S processing of CD46 releases immunoprecipitable cyt1 and cyt2 tail peptides into the cell, is blocked by chemical inhibitors, and is prevented in dominant negative presenilin mutant cell lines. Two human pathogens, Neisseria gonorrhoeae and Neisseria meningitidis, stimulate PS\/\u03b3S processing of CD46-cyt1 and CD46-cyt2. This stimulation requires type IV pili and PilT, the type IV pilus retraction motor, implying that mechanotransduction plays a role in this event. We present a model for PS\/\u03b3S processing of CD46 that provides a mechanism by which signals are transduced via the cyt1 and cyt2 tails to regulate CD46-dependent cellular responses. Our findings have broad implications for understanding the full range of CD46 functions in infection and noninfection situations.<\/jats:p>","DOI":"10.4049\/jimmunol.0900522","type":"journal-article","created":{"date-parts":[[2009,12,16]],"date-time":"2009-12-16T23:16:34Z","timestamp":1261005394000},"page":"694-701","source":"Crossref","is-referenced-by-count":32,"title":["Presenilin\/\u03b3-Secretase Cleaves CD46 in Response to\n                    <i>Neisseria<\/i>\n                    Infection"],"prefix":"10.1093","volume":"184","author":[{"given":"Nathan J","family":"Weyand","sequence":"first","affiliation":[{"name":"BIO5 Institute"},{"name":"Department of Immunobiology, University of Arizona , Tucson, AZ 85721"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M","family":"Calton","sequence":"additional","affiliation":[{"name":"BIO5 Institute"},{"name":"Department of Immunobiology, University of Arizona , Tucson, AZ 85721"},{"name":"Department of Molecular Microbiology and Immunology, Oregon Health and Science University , Portland, OR 97239"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dustin L","family":"Higashi","sequence":"additional","affiliation":[{"name":"BIO5 Institute"},{"name":"Department of Immunobiology, University of Arizona , Tucson, AZ 85721"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen J","family":"Kanack","sequence":"additional","affiliation":[{"name":"Idaho Technology , Salt Lake City, UT 84108"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalene","family":"So","sequence":"additional","affiliation":[{"name":"BIO5 Institute"},{"name":"Department of Immunobiology, University of Arizona , Tucson, AZ 85721"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,27]]},"reference":[{"key":"2026012808092013100_r1","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1146\/annurev.iy.09.040191.002243","article-title":"Membrane cofactor protein (MCP or CD46): newest member of the regulators of complement activation gene cluster.","volume":"9","author":"Liszewski","year":"1991","journal-title":"Annu. Rev. Immunol."},{"key":"2026012808092013100_r2","doi-asserted-by":"crossref","first-page":"6091","DOI":"10.4049\/jimmunol.164.12.6091","article-title":"Cutting edge: CD46, a new costimulatory molecule for T cells, that induces p120CBL and LAT phosphorylation.","volume":"164","author":"Astier","year":"2000","journal-title":"J. Immunol."},{"key":"2026012808092013100_r3","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1002\/eji.200324259","article-title":"CD46-mediated costimulation induces a Th1-biased response and enhances early TCR\/CD3 signaling in human CD4+ T lymphocytes.","volume":"34","author":"S\u00e1nchez","year":"2004","journal-title":"Eur. J. Immunol."},{"key":"2026012808092013100_r4","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1038\/nature01315","article-title":"Activation of human CD4+ cells with CD3 and CD46 induces a T-regulatory cell 1 phenotype.","volume":"421","author":"Kemper","year":"2003","journal-title":"Nature"},{"key":"2026012808092013100_r5","doi-asserted-by":"crossref","first-page":"2840","DOI":"10.1182\/blood-2004-03-0859","article-title":"Differential expression of granzymes A and B in human cytotoxic lymphocyte subsets and T regulatory cells.","volume":"104","author":"Grossman","year":"2004","journal-title":"Blood"},{"key":"2026012808092013100_r6","doi-asserted-by":"crossref","first-page":"18685","DOI":"10.1073\/pnas.0602458103","article-title":"Ligation of the cell surface receptor, CD46, alters T cell polarity and response to antigen presentation.","volume":"103","author":"Oliaro","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026012808092013100_r7","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.4049\/jimmunol.164.4.1839","article-title":"Membrane cofactor protein (MCP; CD46): isoform-specific tyrosine phosphorylation.","volume":"164","author":"Wang","year":"2000","journal-title":"J. Immunol."},{"key":"2026012808092013100_r8","doi-asserted-by":"crossref","first-page":"6780","DOI":"10.4049\/jimmunol.167.12.6780","article-title":"CD46\/CD3 costimulation induces morphological changes of human T cells and activation of Vav, Rac, and extracellular signal-regulated kinase mitogen-activated protein kinase.","volume":"167","author":"Zaffran","year":"2001","journal-title":"J. Immunol."},{"key":"2026012808092013100_r9","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/S1357-2725(99)00092-8","article-title":"Human membrane cofactor protein (MCP, CD46): multiple isoforms and functions.","volume":"31","author":"Seya","year":"1999","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"2026012808092013100_r10","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1093\/oxfordjournals.jbchem.a003203","article-title":"Ligation of human CD46 with purified complement C3b or F(ab\u2019)(2) of monoclonal antibodies enhances isoform-specific interferon \u03b3-dependent nitric oxide production in macrophages.","volume":"132","author":"Hirano","year":"2002","journal-title":"J Biochem"},{"key":"2026012808092013100_r11","doi-asserted-by":"crossref","first-page":"4776","DOI":"10.1128\/JVI.73.6.4776-4785.1999","article-title":"Human CD46 enhances nitric oxide production in mouse macrophages in response to measles virus infection in the presence of \u03b3 interferon: dependence on the CD46 cytoplasmic domains.","volume":"73","author":"Hirano","year":"1999","journal-title":"J. Virol."},{"key":"2026012808092013100_r12","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1038\/ni810","article-title":"Linking innate and acquired immunity: divergent role of CD46 cytoplasmic domains in T cell induced inflammation.","volume":"3","author":"Marie","year":"2002","journal-title":"Nat. Immunol."},{"key":"2026012808092013100_r13","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1126\/science.273.5272.228","article-title":"Mechanism of suppression of cell-mediated immunity by measles virus.","volume":"273","author":"Karp","year":"1996","journal-title":"Science"},{"key":"2026012808092013100_r14","doi-asserted-by":"crossref","first-page":"2877","DOI":"10.1182\/blood-2002-10-3152","article-title":"Selective suppression of IL-12 production by human herpesvirus 6.","volume":"102","author":"Smith","year":"2003","journal-title":"Blood"},{"key":"2026012808092013100_r15","doi-asserted-by":"crossref","first-page":"677","DOI":"10.4049\/jimmunol.175.2.677","article-title":"Induction of a regulatory phenotype in human CD4+ T cells by streptococcal M protein.","volume":"175","author":"Price","year":"2005","journal-title":"J. Immunol."},{"key":"2026012808092013100_r16","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.immuni.2004.09.002","article-title":"Human T regulatory cells can use the perforin pathway to cause autologous target cell death.","volume":"21","author":"Grossman","year":"2004","journal-title":"Immunity"},{"key":"2026012808092013100_r17","doi-asserted-by":"crossref","first-page":"10292","DOI":"10.1128\/JVI.72.12.10292-10297.1998","article-title":"Morbillivirus downregulation of CD46.","volume":"72","author":"Galbraith","year":"1998","journal-title":"J. Virol."},{"key":"2026012808092013100_r18","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1084\/jem.20031159","article-title":"Down-regulation of CD46 by piliated Neisseria gonorrhoeae.","volume":"198","author":"Gill","year":"2003","journal-title":"J. Exp. Med."},{"key":"2026012808092013100_r19","doi-asserted-by":"crossref","first-page":"3951","DOI":"10.1128\/IAI.00109-08","article-title":"CD46 Contributes to the severity of group A streptococcal infection.","volume":"76","author":"L\u00f6vkvist","year":"2008","journal-title":"Infect. Immun."},{"key":"2026012808092013100_r20","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1099\/0022-1317-74-6-1073","article-title":"Measles virus haemagglutinin induces down-regulation of gp57\/67, a molecule involved in virus binding.","volume":"74","author":"Naniche","year":"1993","journal-title":"J. Gen. Virol."},{"key":"2026012808092013100_r21","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1038\/sj.gt.3302946","article-title":"Downregulation of human CD46 by adenovirus serotype 35 vectors.","volume":"14","author":"Sakurai","year":"2007","journal-title":"Gene Ther."},{"key":"2026012808092013100_r22","doi-asserted-by":"crossref","first-page":"46927","DOI":"10.1074\/jbc.M308261200","article-title":"Ligand binding determines whether CD46 is internalized by clathrin-coated pits or macropinocytosis.","volume":"278","author":"Crimeen-Irwin","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2026012808092013100_r23","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/S0092-8674(00)81678-5","article-title":"CD46 is a cellular receptor for human herpesvirus 6.","volume":"99","author":"Santoro","year":"1999","journal-title":"Cell"},{"key":"2026012808092013100_r24","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1146\/annurev.cellbio.16.1.423","article-title":"Interactions of pathogenic neisseriae with epithelial cell membranes.","volume":"16","author":"Merz","year":"2000","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"2026012808092013100_r25","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/35024105","article-title":"Pilus retraction powers bacterial twitching motility.","volume":"407","author":"Merz","year":"2000","journal-title":"Nature"},{"key":"2026012808092013100_r26","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1046\/j.1365-2958.1997.4841857.x","article-title":"Membrane cofactor protein (MCP or CD46) is a cellular pilus receptor for pathogenic Neisseria.","volume":"25","author":"K\u00e4llstr\u00f6m","year":"1997","journal-title":"Mol. Microbiol."},{"key":"2026012808092013100_r27","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1083\/jcb.200109005","article-title":"CD46 is phosphorylated at tyrosine 354 upon infection of epithelial cells by Neisseria gonorrhoeae.","volume":"156","author":"Lee","year":"2002","journal-title":"J. Cell Biol."},{"key":"2026012808092013100_r28","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1111\/j.1462-5822.2005.00584.x","article-title":"Release of host-derived membrane vesicles following pilus-mediated adhesion of Neisseria gonorrhoeae.","volume":"7","author":"Gill","year":"2005","journal-title":"Cell. Microbiol."},{"key":"2026012808092013100_r29","doi-asserted-by":"crossref","first-page":"2428","DOI":"10.1128\/IAI.74.4.2428-2435.2006","article-title":"Monoclonal antibody detection of CD46 clustering beneath Neisseria gonorrhoeae microcolonies.","volume":"74","author":"Weyand","year":"2006","journal-title":"Infect. Immun."},{"key":"2026012808092013100_r30","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.tig.2007.01.008","article-title":"Presenilin diversifies its portfolio.","volume":"23","author":"Parks","year":"2007","journal-title":"Trends Genet."},{"key":"2026012808092013100_r31","first-page":"194","article-title":"Presenilins: members of the \u03b3-secretase quartets, but part-time soloists too.","volume":"23","author":"Wakabayashi","year":"2008","journal-title":"Physiology (Bethesda)"},{"key":"2026012808092013100_r32","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1007\/s00018-008-7462-2","article-title":"Substrate specificity of \u03b3-secretase and other intramembrane proteases.","volume":"65","author":"Beel","year":"2008","journal-title":"Cell. Mol. Life Sci."},{"key":"2026012808092013100_r33","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/19083","article-title":"A presenilin-1-dependent \u03b3-secretase-like protease mediates release of Notch intracellular domain.","volume":"398","author":"De Strooper","year":"1999","journal-title":"Nature"},{"key":"2026012808092013100_r34","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1038\/sj.onc.1206298","article-title":"Presenilin-dependent \u03b3-secretase activity mediates the intramembranous cleavage of CD44.","volume":"22","author":"Murakami","year":"2003","journal-title":"Oncogene"},{"key":"2026012808092013100_r35","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1126\/science.1065412","article-title":"\u03b3 -Secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase.","volume":"294","author":"Ni","year":"2001","journal-title":"Science"},{"key":"2026012808092013100_r36","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/34910","article-title":"Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein.","volume":"391","author":"De Strooper","year":"1998","journal-title":"Nature"},{"key":"2026012808092013100_r37","doi-asserted-by":"crossref","first-page":"147","DOI":"10.2174\/156720508783954677","article-title":"The catalytic core of \u03b3-secretase: presenilin revisited.","volume":"5","author":"Steiner","year":"2008","journal-title":"Curr. Alzheimer Res."},{"key":"2026012808092013100_r38","doi-asserted-by":"crossref","first-page":"22475","DOI":"10.1074\/jbc.M300974200","article-title":"Presenilin-1 and presenilin-2 exhibit distinct yet overlapping \u03b3-secretase activities.","volume":"278","author":"Lai","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2026012808092013100_r39","doi-asserted-by":"crossref","first-page":"7513","DOI":"10.1523\/JNEUROSCI.16-23-07513.1996","article-title":"Expression of presenilin 1 and 2 (PS1 and PS2) in human and murine tissues.","volume":"16","author":"Lee","year":"1996","journal-title":"J. Neurosci."},{"key":"2026012808092013100_r40","doi-asserted-by":"crossref","first-page":"24601","DOI":"10.1074\/jbc.M402248200","article-title":"Dissection of amyloid-\u03b2 precursor protein-dependent transcriptional transactivation.","volume":"279","author":"Cao","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2026012808092013100_r41","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/S0898-6568(03)00041-X","article-title":"RIPped out by presenilin-dependent \u03b3-secretase.","volume":"15","author":"Medina","year":"2003","journal-title":"Cell. Signal."},{"key":"2026012808092013100_r42","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1016\/j.molimm.2005.11.015","article-title":"Complement regulator loss on apoptotic neuronal cells causes increased complement activation and promotes both phagocytosis and cell lysis.","volume":"43","author":"Cole","year":"2006","journal-title":"Mol. Immunol."},{"key":"2026012808092013100_r43","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1002\/eji.200424969","article-title":"Complement inhibitor membrane cofactor protein (MCP; CD46) is constitutively shed from cancer cell membranes in vesicles and converted by a metalloproteinase to a functionally active soluble form.","volume":"34","author":"Hakulinen","year":"2004","journal-title":"Eur. J. Immunol."},{"key":"2026012808092013100_r44","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1046\/j.1365-2567.2002.01468.x","article-title":"Loxosceles spider venom induces metalloproteinase mediated cleavage of MCP\/CD46 and MHCI and induces protection against C-mediated lysis.","volume":"107","author":"Van Den Berg","year":"2002","journal-title":"Immunology"},{"key":"2026012808092013100_r45","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1095\/biolreprod57.4.847","article-title":"Generation of papillomavirus-immortalized cell lines from normal human ectocervical, endocervical, and vaginal epithelium that maintain expression of tissue-specific differentiation proteins.","volume":"57","author":"Fichorova","year":"1997","journal-title":"Biol. Reprod."},{"key":"2026012808092013100_r46","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1165\/ajrcmb.10.1.7507342","article-title":"CFTR expression and chloride secretion in polarized immortal human bronchial epithelial cells.","volume":"10","author":"Cozens","year":"1994","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2026012808092013100_r47","doi-asserted-by":"crossref","first-page":"26277","DOI":"10.1074\/jbc.M002812200","article-title":"Presenilin 1 regulates pharmacologically distinct \u03b3 -secretase activities. Implications for the role of presenilin in \u03b3 -secretase cleavage.","volume":"275","author":"Murphy","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2026012808092013100_r48","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1111\/j.1471-4159.2004.02858.x","article-title":"Presenilin 2 familial Alzheimer\u2019s disease mutations result in partial loss of function and dramatic changes in Abeta 42\/40 ratios.","volume":"92","author":"Walker","year":"2005","journal-title":"J. Neurochem."},{"key":"2026012808092013100_r49","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.nbd.2004.04.018","article-title":"Mutations in APP have independent effects on Abeta and CTFgamma generation.","volume":"17","author":"Hecimovic","year":"2004","journal-title":"Neurobiol. Dis."},{"key":"2026012808092013100_r50","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1073\/pnas.93.4.1683","article-title":"Signal transduction by activated mNotch: importance of proteolytic processing and its regulation by the extracellular domain.","volume":"93","author":"Kopan","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026012808092013100_r51","doi-asserted-by":"crossref","first-page":"13075","DOI":"10.1073\/pnas.1735338100","article-title":"A presenilin dimer at the core of the \u03b3-secretase enzyme: insights from parallel analysis of Notch 1 and APP proteolysis.","volume":"100","author":"Schroeter","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026012808092013100_r52","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1073\/pnas.83.7.2177","article-title":"Antigenic variation of gonococcal pilus involves assembly of separated silent gene segments.","volume":"83","author":"Segal","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026012808092013100_r53","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1046\/j.1462-5822.2001.00112.x","article-title":"The pilus-induced Ca2+ flux triggers lysosome exocytosis and increases the amount of Lamp1 accessible to Neisseria IgA1 protease.","volume":"3","author":"Ayala","year":"2001","journal-title":"Cell. Microbiol."},{"key":"2026012808092013100_r54","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1007\/BF03401658","article-title":"Traversal of a polarized epithelium by pathogenic Neisseriae: facilitation by type IV pili and maintenance of epithelial barrier function.","volume":"2","author":"Merz","year":"1996","journal-title":"Mol. Med."},{"key":"2026012808092013100_r55","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1111\/j.1462-5822.2005.00551.x","article-title":"PilT is required for PI(3,4,5)P3-mediated crosstalk between Neisseria gonorrhoeae and epithelial cells.","volume":"7","author":"Lee","year":"2005","journal-title":"Cell. Microbiol."},{"key":"2026012808092013100_r56","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1046\/j.1365-2958.1998.00935.x","article-title":"PilT mutations lead to simultaneous defects in competence for natural transformation and twitching motility in piliated Neisseria gonorrhoeae.","volume":"29","author":"Wolfgang","year":"1998","journal-title":"Mol. Microbiol."},{"key":"2026012808092013100_r57","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1111\/j.1365-2958.1993.tb01615.x","article-title":"Antigenic variation of pilin regulates adhesion of Neisseria meningitidis to human epithelial cells.","volume":"8","author":"Nassif","year":"1993","journal-title":"Mol. Microbiol."},{"key":"2026012808092013100_r58","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1084\/jem.168.2.507","article-title":"Purification and characterization of eight class 5 outer membrane protein variants from a clone of Neisseria meningitidis serogroup A.","volume":"168","author":"Achtman","year":"1988","journal-title":"J. Exp. Med."},{"key":"2026012808092013100_r59","doi-asserted-by":"crossref","first-page":"4341","DOI":"10.1128\/iai.65.10.4341-4349.1997","article-title":"Attachment of piliated, Opa- and Opc- gonococci and meningococci to epithelial cells elicits cortical actin rearrangements and clustering of tyrosine-phosphorylated proteins.","volume":"65","author":"Merz","year":"1997","journal-title":"Infect. Immun."},{"key":"2026012808092013100_r60","first-page":"10.8.1","volume-title":"Current Protocols in Molecular Biology","year":"2008"},{"key":"2026012808092013100_r61","doi-asserted-by":"crossref","first-page":"4415","DOI":"10.4049\/jimmunol.156.11.4415","article-title":"Membrane cofactor protein (MCP; CD46). Isoforms differ in protection against the classical pathway of complement.","volume":"156","author":"Liszewski","year":"1996","journal-title":"J. Immunol."},{"key":"2026012808092013100_r62","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1046\/j.1365-2958.1999.01459.x","article-title":"Type IV pili of pathogenic Neisseriae elicit cortical plaque formation in epithelial cells.","volume":"32","author":"Merz","year":"1999","journal-title":"Mol. Microbiol."},{"key":"2026012808092013100_r63","doi-asserted-by":"crossref","first-page":"5965","DOI":"10.1128\/IAI.70.11.5965-5971.2002","article-title":"Neisseria gonorrhoeae porin P1.B induces endosome exocytosis and a redistribution of Lamp1 to the plasma membrane.","volume":"70","author":"Ayala","year":"2002","journal-title":"Infect. Immun."},{"key":"2026012808092013100_r64","doi-asserted-by":"crossref","first-page":"4743","DOI":"10.1128\/IAI.00687-07","article-title":"Dynamics of Neisseria gonorrhoeae attachment: microcolony development, cortical plaque formation, and cytoprotection.","volume":"75","author":"Higashi","year":"2007","journal-title":"Infect. Immun."},{"key":"2026012808092013100_r65","doi-asserted-by":"crossref","first-page":"e100","DOI":"10.1371\/journal.pbio.0030100","article-title":"The N. gonorrhoeae type IV pilus stimulates mechanosensitive pathways and cytoprotection through a pilT-dependent mechanism.","volume":"3","author":"Howie","year":"2005","journal-title":"PLoS Biol."},{"key":"2026012808092013100_r66","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1128\/IAI.00153-08","article-title":"Extracellular signal-regulated kinase activation by Neisseria gonorrhoeae downregulates epithelial cell proapoptotic proteins Bad and Bim.","volume":"76","author":"Howie","year":"2008","journal-title":"Infect. Immun."},{"key":"2026012808092013100_r67","doi-asserted-by":"crossref","first-page":"3173","DOI":"10.1074\/jbc.275.5.3173","article-title":"The transmembrane aspartates in presenilin 1 and 2 are obligatory for \u03b3-secretase activity and amyloid \u03b2-protein generation.","volume":"275","author":"Kimberly","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2026012808092013100_r68","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/nrm910","article-title":"\u03b3-secretase-mediated proteolysis in cell-surface-receptor signalling.","volume":"3","author":"Fortini","year":"2002","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2026012808092013100_r69","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.semcdb.2008.11.014","article-title":"Presenilin: RIP and beyond.","volume":"20","author":"Hass","year":"2009","journal-title":"Semin. Cell Dev. Biol."},{"key":"2026012808092013100_r70","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1111\/j.1462-5822.2004.00497.x","article-title":"Engagement of CD46 and alpha5beta1 integrin by group A streptococci is required for efficient invasion of epithelial cells.","volume":"7","author":"Rezcallah","year":"2005","journal-title":"Cell. Microbiol."},{"key":"2026012808092013100_r71","doi-asserted-by":"crossref","first-page":"e87","DOI":"10.1371\/journal.pbio.0060087","article-title":"Cooperative retraction of bundled type IV pili enables nanonewton force generation.","volume":"6","author":"Biais","year":"2008","journal-title":"PLoS Biol."},{"key":"2026012808092013100_r72","doi-asserted-by":"crossref","first-page":"6901","DOI":"10.1073\/pnas.121171698","article-title":"Direct observation of extension and retraction of type IV pili.","volume":"98","author":"Skerker","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026012808092013100_r73","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/nsmb1190","article-title":"Adenovirus type 11 binding alters the conformation of its receptor CD46.","volume":"14","author":"Persson","year":"2007","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2026012808092013100_r74","doi-asserted-by":"crossref","first-page":"e268","DOI":"10.1371\/journal.pbio.0050268","article-title":"Force-induced unfolding of fibronectin in the extracellular matrix of living cells.","volume":"5","author":"Smith","year":"2007","journal-title":"PLoS Biol."},{"key":"2026012808092013100_r75","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1111\/j.1600-0854.2007.00592.x","article-title":"Notch signaling\u2014constantly on the move.","volume":"8","author":"Nichols","year":"2007","journal-title":"Traffic"},{"key":"2026012808092013100_r76","doi-asserted-by":"crossref","first-page":"47329","DOI":"10.1074\/jbc.M107666200","article-title":"The angiogenic factor Cyr61 activates a genetic program for wound healing in human skin fibroblasts.","volume":"276","author":"Chen","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2026012808092013100_r77","doi-asserted-by":"crossref","first-page":"4477","DOI":"10.1074\/jbc.M108479200","article-title":"A functional interaction between CD46 and DLG4: a role for DLG4 in epithelial polarization.","volume":"277","author":"Ludford-Menting","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2026012808092013100_r78","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0896-6273(03)00205-8","article-title":"Aph-1, Pen-2, and Nicastrin with Presenilin generate an active \u03b3-Secretase complex.","volume":"38","author":"De Strooper","year":"2003","journal-title":"Neuron"},{"key":"2026012808092013100_r79","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1083\/jcb.200403155","article-title":"The ERBB4\/HER4 receptor tyrosine kinase regulates gene expression by functioning as a STAT5A nuclear chaperone.","volume":"167","author":"Williams","year":"2004","journal-title":"J. Cell Biol."},{"key":"2026012808092013100_r80","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/30756","article-title":"Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain.","volume":"393","author":"Schroeter","year":"1998","journal-title":"Nature"},{"key":"2026012808092013100_r81","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nrm1406","article-title":"\u03b3-secretase: proteasome of the membrane?","volume":"5","author":"Kopan","year":"2004","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2026012808092013100_r82","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1523\/JNEUROSCI.3850-04.2005","article-title":"Presenilin attenuates receptor-mediated signaling and synaptic function.","volume":"25","author":"Parent","year":"2005","journal-title":"J. Neurosci."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/184\/2\/694\/62717887\/ji_0900522.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/184\/2\/694\/62717887\/ji_0900522.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T13:10:36Z","timestamp":1769605836000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/184\/2\/694\/8013503"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,12,27]]},"references-count":82,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2009,12,27]]},"published-print":{"date-parts":[[2010,1,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.0900522","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2010,1]]},"published":{"date-parts":[[2009,12,27]]}}}