Release of FGF1 and p40 synaptotagmin 1 correlates with their membrane destabilizing ability.
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.
Graziani
Irene
I
Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA.
Bagalá
Cinzia
C
Duarte
Maria
M
Soldi
Raffaella
R
Kolev
Vihren
V
Tarantini
Francesca
F
Kumar
Thallapuranam Krishnaswamy Suresh
TK
Doyle
Andrew
A
Neivandt
David
D
Yu
Chin
C
Maciag
Thomas
T
Prudovsky
Igor
I
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*
D008051:Lipid Bilayers; D008081:Liposomes; D011994:Recombinant Proteins; C494310:SYT1 protein, human; D050863:Synaptotagmin I; D016220:Fibroblast Growth Factor 1