{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:15:53Z","timestamp":1791080153908,"version":"4.1.0"},"reference-count":46,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,3,10]]},"abstract":"<jats:p>Cells that express wild-type influenza hemagglutinin (HA) fully fuse to RBCs, while cells that express the HA-ectodomain anchored to membranes by glycosylphosphatidylinositol, rather than by a transmembrane domain, only hemifuse to RBCs. Amphipaths were inserted into inner and outer membrane leaflets to determine the contribution of each leaflet in the transition from hemifusion to fusion. When inserted into outer leaflets, amphipaths did not promote the transition, independent of whether the agent induces monolayers to bend outward (conferring positive spontaneous monolayer curvature) or inward (negative curvature). In contrast, when incorporated into inner leaflets, positive curvature agents led to full fusion. This suggests that fusion is completed when a lipidic fusion pore with net positive curvature is formed by the inner leaflets that compose a hemifusion diaphragm. Suboptimal fusion conditions were established for RBCs bound to cells expressing wild-type HA so that lipid but not aqueous dye spread was observed. While this is the same pattern of dye spread as in stable hemifusion, for this \u201cstunted\u201d fusion, lower concentrations of amphipaths in inner leaflets were required to promote transfer of aqueous dyes. Also, these amphipaths induced larger pores for stunted fusion than they generated within a stable hemifusion diaphragm. Therefore, spontaneous curvature of inner leaflets can affect formation and enlargement of fusion pores induced by HA. We propose that after the HA-ectodomain induces hemifusion, the transmembrane domain causes pore formation by conferring positive spontaneous curvature to leaflets of the hemifusion diaphragm.<\/jats:p>","DOI":"10.1083\/jcb.136.5.995","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:46:23Z","timestamp":1027701983000},"page":"995-1005","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":148,"title":["Inner but Not Outer Membrane Leaflets Control the Transition from Glycosylphosphatidylinositol-anchored Influenza Hemagglutinin-induced Hemifusion to Full Fusion"],"prefix":"10.1083","volume":"136","author":[{"given":"Grigory B.","family":"Melikyan","sequence":"first","affiliation":[{"name":"Department of Molecular Biophysics and Physiology, Rush Medical College, Chicago, Illinois 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofya A.","family":"Brener","sequence":"additional","affiliation":[{"name":"Department of Molecular Biophysics and Physiology, Rush Medical College, Chicago, Illinois 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong C.","family":"Ok","sequence":"additional","affiliation":[{"name":"Department of Molecular Biophysics and Physiology, Rush Medical College, Chicago, Illinois 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredric S.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Molecular Biophysics and Physiology, Rush Medical College, Chicago, Illinois 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1997,3,10]]},"reference":[{"key":"2023072206374859700_B1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0302-4598(79)85005-9","article-title":"Electrical breakdown of BLM: main experimental facts and their qualitative discussion","volume":"6","author":"Abidor","year":"1979","journal-title":"Bioelectrochem Bioenerg"},{"key":"2023072206374859700_B2","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1016\/S0006-3495(94)80995-6","article-title":"Adsorption of surfactants by membranes: erythrocytes versus synthetic vesicles","volume":"66","author":"Binford","year":"1994","journal-title":"Biophys J"},{"key":"2023072206374859700_B3","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1073\/pnas.73.2.452","article-title":"Amphipathic amines affect membrane excitability in Paramecium: role of bilayer couple","volume":"73","author":"Browning","year":"1976","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023072206374859700_B4","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/0304-4157(87)90016-5","article-title":"Biomembrane fusion: a new concept derived from model studies using two interacting planar lipid bilayers","volume":"906","author":"Chernomordik","year":"1987","journal-title":"Biochim Biophys Acta"},{"key":"2023072206374859700_B5","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/0014-5793(93)81330-3","article-title":"Lysolipids reversibly inhibit Ca2+-, GTP- and pH- dependent fusion of biological membranes","volume":"318","author":"Chernomordik","year":"1993","journal-title":"FEBS Lett"},{"key":"2023072206374859700_B6","doi-asserted-by":"crossref","first-page":"7115","DOI":"10.1128\/jvi.68.11.7115-7123.1994","article-title":"An amphipathic peptide from the C-terminal region of the Human Immunodeficiency Virus envelope glycoprotein causes pore formation in membranes","volume":"68","author":"Chernomordik","year":"1994","journal-title":"J Virol"},{"key":"2023072206374859700_B7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF00232676","article-title":"Lipids in biological membrane fusion","volume":"146","author":"Chernomordik","year":"1995","journal-title":"J Membr Biol"},{"key":"2023072206374859700_B8","doi-asserted-by":"crossref","first-page":"3049","DOI":"10.1128\/jvi.69.5.3049-3058.1995","article-title":"Control of Baculovirus gp64-induced syncytium formation by membrane lipid composition","volume":"69","author":"Chernomordik","year":"1995","journal-title":"J Virol"},{"key":"2023072206374859700_B9","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/S0006-3495(95)79966-0","article-title":"The hemifusion intermediate and its conversion to complete fusion: regulation by membrane composition","volume":"69","author":"Chernomordik","year":"1995","journal-title":"Biophys J"},{"key":"2023072206374859700_B10","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1128\/jvi.65.5.2402-2407.1991","article-title":"Delay time for influenza virus hemagglutinin-induced membrane fusion depends on hemagglutinin surface density","volume":"65","author":"Clague","year":"1991","journal-title":"J Virol"},{"key":"2023072206374859700_B11","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1083\/jcb.133.3.559","article-title":"Membrane fusion mediated by the influenza virus hemagglutinin requires the concerted action of at least three hemagglutinin trimers","volume":"133","author":"Danieli","year":"1996","journal-title":"J Cell Biol"},{"key":"2023072206374859700_B12","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/0005-2736(68)90078-3","article-title":"Transformation and restoration of biconcave shape of human erythrocytes induced by amphipathic agents and changes in ionic environment","volume":"163","author":"Deuticke","year":"1968","journal-title":"Biochim Biophys Acta"},{"key":"2023072206374859700_B13","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0091-679X(08)61607-6","article-title":"Delivery of macromolecules into cells expressing a viral membrane fusion protein","volume":"31","author":"Ellens","year":"1989","journal-title":"Methods Cell Biol"},{"key":"2023072206374859700_B14","doi-asserted-by":"crossref","first-page":"9697","DOI":"10.1021\/bi00493a027","article-title":"Fusion of influenza hemagglutinin-expressing fibroblasts with glycoprotein-bearing liposomes: role of hemagglutinin surface density","volume":"29","author":"Ellens","year":"1990","journal-title":"Biochemistry"},{"key":"2023072206374859700_B15","doi-asserted-by":"crossref","first-page":"7092","DOI":"10.1021\/bi00346a011","article-title":"Diacylglycerols, lysolecithin, or hydrocarbons markedly alter the bilayer to hexagonal phase transition temperature of phosphatidylethanolamines","volume":"24","author":"Epand","year":"1985","journal-title":"Biochemistry"},{"key":"2023072206374859700_B16","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/0009-3084(91)90051-C","article-title":"Promotion of hexagonal phase formation and lipid mixing by fatty acids with varying degrees of unsaturation","volume":"57","author":"Epand","year":"1991","journal-title":"Chem Phys Lipids"},{"key":"2023072206374859700_B17","doi-asserted-by":"crossref","first-page":"29279","DOI":"10.1074\/jbc.270.49.29279","article-title":"Inhibition of influenza-induced membrane fusion by lysophosphatidylcholine","volume":"270","author":"G\u00fcnter-Ausborn","year":"1995","journal-title":"J Biol Chem"},{"key":"2023072206374859700_B18","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/0005-2736(81)90533-2","article-title":"The role of nonbilayer lipid structures in the fusion of human erythrocytes induced by lipid fusogens","volume":"640","author":"Hope","year":"1981","journal-title":"Biochim Biophys Acta"},{"key":"2023072206374859700_B19","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/0005-2736(81)90256-X","article-title":"Influence of local and neutral anaesthetics on the polymorphic phase preferences of egg yolk phosphatidylethanolamine","volume":"647","author":"Hornby","year":"1981","journal-title":"Biochim Biophys Acta"},{"key":"2023072206374859700_B20","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/0092-8674(94)90344-1","article-title":"Lipid-anchored influenza hemagglutinin promotes hemifusion, not complete fusion","volume":"76","author":"Kemble","year":"1994","journal-title":"Cell"},{"key":"2023072206374859700_B21","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/BF00254765","article-title":"Stalk mechanism of membrane fusion","volume":"17","author":"Kozlov","year":"1989","journal-title":"Eur Biophys J"},{"key":"2023072206374859700_B22","doi-asserted-by":"crossref","first-page":"9225","DOI":"10.1016\/S0021-9258(17)47289-9","article-title":"Interaction of chlorpromazine with the human erythrocyte membrane","volume":"259","author":"Lieber","year":"1984","journal-title":"J Biol Chem"},{"key":"2023072206374859700_B23","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/0005-2736(86)90044-1","article-title":"Trifluoperazine inhibits Sendai virus-induced hemolysis","volume":"856","author":"MacDonald","year":"1986","journal-title":"Biochim Biophys Acta"},{"key":"2023072206374859700_B24","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1085\/jgp.106.5.783","article-title":"The fusion kinetics of influenza hemagglutinin expressing cells to planar bilayer membranes is affected by HA density and host cell surface","volume":"106","author":"Melikyan","year":"1995","journal-title":"J Gen Physiol"},{"key":"2023072206374859700_B25","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1083\/jcb.131.3.679","article-title":"GPI-anchored influenza hemagglutinin induces hemifusion to both red blood cell and planar bilayer membranes","volume":"131","author":"Melikyan","year":"1995","journal-title":"J Cell Biol"},{"key":"2023072206374859700_B26","doi-asserted-by":"crossref","first-page":"3972","DOI":"10.1016\/S0021-9258(19)84948-7","article-title":"Kinetics of pH - dependent fusion between 3T3 fibroblasts expressing influenza hemagglutinin and red blood cells","volume":"264","author":"Morris","year":"1989","journal-title":"J Biol Chem"},{"key":"2023072206374859700_B27"},{"key":"2023072206374859700_B28","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1083\/jcb.109.1.113","article-title":"Initial stages of influenza hemagglutinin-induced cell fusion monitored simultaneously by two fluorescent events: cytoplasmic continuity and lipid mixing","volume":"109","author":"Sarkar","year":"1989","journal-title":"J Cell Biol"},{"key":"2023072206374859700_B29","doi-asserted-by":"crossref","first-page":"9267","DOI":"10.1016\/S0021-9258(18)98345-6","article-title":"Role of the fusion peptide sequence in initial stage of influenza hemagglutinin-induced cell fusion","volume":"268","author":"Schoch","year":"1993","journal-title":"J Biol Chem"},{"key":"2023072206374859700_B30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0304-4157(90)90002-T","article-title":"Structure of the inverted hexagonal (HII) phase, and nonlamellar phase transitions of lipids","volume":"1031","author":"Seddon","year":"1990","journal-title":"Biochim Biophys Acta"},{"key":"2023072206374859700_B31","first-page":"583","article-title":"The membrane action of anesthetics and tranquilizers","volume":"24","author":"Seeman","year":"1972","journal-title":"Pharmacol Rev"},{"key":"2023072206374859700_B32","doi-asserted-by":"crossref","first-page":"4956","DOI":"10.1021\/bi9526903","article-title":"Influenza virus-liposome lipid mixing is leaky and largely insensitive to the material properties of the target membrane","volume":"35","author":"Shangguan","year":"1996","journal-title":"Biochemistry"},{"key":"2023072206374859700_B33","doi-asserted-by":"crossref","first-page":"4457","DOI":"10.1073\/pnas.71.11.4457","article-title":"Biological membranes as bilayer couples. A molecular mechanism of drug-erythrocyte interactions","volume":"71","author":"Sheetz","year":"1974","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023072206374859700_B34"},{"key":"2023072206374859700_B35"},{"key":"2023072206374859700_B36","doi-asserted-by":"crossref","first-page":"4231","DOI":"10.1002\/j.1460-2075.1990.tb07871.x","article-title":"Intermediates in influenza induced membrane fusion","volume":"9","author":"Stegmann","year":"1990","journal-title":"EMBO (Eur Mol Biol Organ) J"},{"key":"2023072206374859700_B37","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0302-4598(82)80169-4","article-title":"Effects of UO22+ions on the properties of bilayer lipid membranes","volume":"9","author":"Sukharev","year":"1982","journal-title":"Bioelectrochem Bioenerg"},{"key":"2023072206374859700_B38"},{"key":"2023072206374859700_B39","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/j.1749-6632.1987.tb48657.x","article-title":"Lipid polymorphism","volume":"492","author":"Tilcock","year":"1987","journal-title":"Ann NY Acad Sci"},{"key":"2023072206374859700_B40","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1083\/jcb.121.3.543","article-title":"Membrane flux through the pore formed by a fusogenic viral envelope protein during cell fusion","volume":"121","author":"Tse","year":"1993","journal-title":"J Cell Biol"},{"key":"2023072206374859700_B41","doi-asserted-by":"crossref","first-page":"25764","DOI":"10.1016\/S0021-9258(19)74455-X","article-title":"Lysophosphatidylcholine reversibly arrests exocytosis and viral fusion at a stage between triggering and membrane merger","volume":"268","author":"Vogel","year":"1993","journal-title":"J Biol Chem"},{"key":"2023072206374859700_B42","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0042-6822(86)90083-8","article-title":"Studies of influenza haemagglutinin-mediated membrane fusion","volume":"149","author":"Wharton","year":"1986","journal-title":"Virology"},{"key":"2023072206374859700_B43","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1126\/science.1439803","article-title":"Membrane fusion","volume":"258","author":"White","year":"1992","journal-title":"Science (Wash DC)"},{"key":"2023072206374859700_B44","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/0005-2736(88)90263-5","article-title":"Biphasic nature of the binding of cationic amphipaths with artificial and biological membranes","volume":"937","author":"Zachowski","year":"1988","journal-title":"Biochim Biophys Acta"},{"key":"2023072206374859700_B45","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1111\/j.1749-6632.1991.tb36501.x","article-title":"A lipid\/protein complex hypothesis for exocytotic fusion pore formation","volume":"635","author":"Zimmerberg","year":"1991","journal-title":"Ann NY Acad Sci"},{"key":"2023072206374859700_B46","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1083\/jcb.127.6.1885","article-title":"Restricted movement of lipid and aqueous dyes through pores formed by influenza hemagglutinin during cell fusion","volume":"127","author":"Zimmerberg","year":"1994","journal-title":"J Cell Biol"}],"container-title":["The Journal of Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jcb\/article-pdf\/136\/5\/995\/1481539\/18994.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jcb\/article-pdf\/136\/5\/995\/1481539\/18994.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,22]],"date-time":"2023-07-22T06:38:42Z","timestamp":1690007922000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jcb\/article\/136\/5\/995\/566\/Inner-but-Not-Outer-Membrane-Leaflets-Control-the"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,3,10]]},"references-count":46,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1997,3,10]]}},"URL":"https:\/\/doi.org\/10.1083\/jcb.136.5.995","relation":{},"ISSN":["0021-9525","1540-8140"],"issn-type":[{"value":"0021-9525","type":"print"},{"value":"1540-8140","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,3,10]]}}}