title: Release of FGF1 and p40 synaptotagmin 1 correlates with their membrane destabilizing ability.
abstract: Fibroblast growth factor (FGF)1 is released from cells as a constituent of a complex that contains the small calcium binding protein S100A13, and the p40 kDa form of synaptotagmin (Syt)1, through an ER-Golgi-independent stress-induced pathway. FGF1 and the other components of its secretory complex are signal peptide-less proteins. We examined their capability to interact with lipid bilayers by studying protein-induced carboxyfluorescein release from liposomes of different phospholipid (pL) compositions. FGF1, p40 Syt1, and S100A13 induced destabilization of liposomes composed of acidic but not of zwitterionic pL. We produced mutants of FGF1 and p40 Syt1, in which specific basic amino acid residues in the regions that bind acidic pL were substituted. The ability of these mutants to induce liposomes destabilization was strongly attenuated, and they exhibited drastically diminished spontaneous and stress-induced release. Apparently, the non-classical release of FGF1 and p40 Syt1 involves destabilization of membranes containing acidic pL.
authors.affiliation: Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA.
authors.forename: Irene
authors.initials: I
authors.lastname: Graziani
authors.forename: Cinzia
authors.initials: C
authors.lastname: Bagalá
authors.forename: Maria
authors.initials: M
authors.lastname: Duarte
authors.forename: Raffaella
authors.initials: R
authors.lastname: Soldi
authors.forename: Vihren
authors.initials: V
authors.lastname: Kolev
authors.forename: Francesca
authors.initials: F
authors.lastname: Tarantini
authors.forename: Thallapuranam Krishnaswamy Suresh
authors.initials: TK
authors.lastname: Kumar
authors.forename: Andrew
authors.initials: A
authors.lastname: Doyle
authors.forename: David
authors.initials: D
authors.lastname: Neivandt
authors.forename: Chin
authors.initials: C
authors.lastname: Yu
authors.forename: Thomas
authors.initials: T
authors.lastname: Maciag
authors.forename: Igor
authors.initials: I
authors.lastname: Prudovsky
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D016220:Fibroblast Growth Factor 1 / Q000737:chemistry*; D006056:Golgi Apparatus / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D051379:Mice; D008954:Models, Biological; D041681:NIH 3T3 Cells; D011994:Recombinant Proteins / Q000737:chemistry; D050863:Synaptotagmin I / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D008081:Liposomes; D011994:Recombinant Proteins; C494310:SYT1 protein, human; D050863:Synaptotagmin I; D016220:Fibroblast Growth Factor 1