Release of FGF1 and p40 synaptotagmin 1 correlates with their membrane destabilizing ability.

Irene Graziani

Cinzia Bagalá

Maria Duarte

Raffaella Soldi

David Neivandt+3 authors

^{Maine Medical Center Research Institute, Scarborough, Maine 04074, USA}

^{Department of Critical Care Medicine and Surgery, Gerontology and Geriatrics Unit, University of Florence, Florence 50139, Italy}

^{Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AZ 72701, USA}

^{Department of Chemical and Biological Engineering, and Functional Genomics Program, University of Maine, Orono, ME 04469 USA}

^{Department of Chemistry, National Tsing Hua University, Hsinchu 30043, Taiwan}

* To whom correspondence should be addressed. Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough ME 04074. Telephone: 207-885-8146; Fax 201-885-8179; Email: gro.cmm@iodurp

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.

Keywords: FGF1, synaptotagmin 1, S100A13, non-classical release, membrane, phospholipid

Abbreviations: 5,6 carboxyfluorescein (CF); fibroblast growth factor (FGF); molten globule (MG); phospholipid (pL); phosphatidylinositol (pI); phosphatidylserine (pS); phosphatidylglycerol (pG); phosphatidylcholine (pC); synaptotagmin (Syt); wild type (WT)

Abstract

Footnotes

The article is dedicated to the memory of Tom Maciag, friend, scientist, and mentor.

Footnotes

References

1. Bottcher RT, Niehrs CFibroblast growth factor signaling during early vertebrate development. Endocr Rev. 2005;26:63–77.[PubMed][Google Scholar]
2. Friesel R, Maciag TFibroblast growth factor prototype release and fibroblast growth factor receptor signaling. Thromb Haemost. 1999;82:748–754.[PubMed][Google Scholar]
3. Dailey L, Ambrosetti D, Mansukhani A, Basilico CMechanisms underlying differential responses to FGF signaling. Cytokine Growth Factor Rev. 2005;16:233–247.[PubMed][Google Scholar]
4. Nickel WUnconventional secretory routes: direct protein export across the plasma membrane of mammalian cells. Traffic. 2005;6:607–614.[PubMed][Google Scholar]
5. Florkiewicz RZ, Majack RA, Buechler RD, Florkiewicz EQuantitative export of FGF-2 occurs through an alternative, energy- dependent, non-ER/Golgi pathway. J Cell Physiol. 1995;162:388–399.[PubMed][Google Scholar]
6. Mignatti P, Morimoto T, Rifkin DBBasic fibroblast growth factor, a protein devoid of secretory signal sequence, is released by cells via a pathway independent of the endoplasmic reticulum-Golgi complex. J Cell Physiol. 1992;151:81–93.[PubMed][Google Scholar]
7. Andrei C, Dazzi C, Lotti L, Torrisi MR, Chimini G, Rubartelli AThe secretory route of the leaderless protein interleukin 1beta involves exocytosis of endolysosome-related vesicles. Mol Biol Cell. 1999;10:1463–1475.[Google Scholar]
8. Andrei C, Margiocco P, Poggi A, Lotti LV, Torrisi MR, Rubartelli APhospholipases C and A2 control lysosome-mediated IL-1 beta secretion: Implications for inflammatory processes. Proc Natl Acad Sci U S A. 2004;101:9745–9750.[Google Scholar]
9. Hunter-Lavin C, Davies EL, Bacelar MM, Marshall MJ, Andrew SM, Williams JHHsp70 release from peripheral blood mononuclear cells. Biochem Biophys Res Commun. 2004;324:511–517.[PubMed][Google Scholar]
10. Jeske NA, Glucksman MJ, Roberts JLMetalloendopeptidase EC3.4.24.15 is constitutively released from the exofacial leaflet of lipid rafts in GT1-7 cells. J Neurochem. 2004;90:819–828.[PubMed][Google Scholar]
11. Lee SJ, Saravanan RS, Damasceno CM, Yamane H, Kim BD, Rose JKDigging deeper into the plant cell wall proteome. Plant Physiol Biochem. 2004;42:979–988.[PubMed][Google Scholar]
12. Prudovsky I, Mandinova A, Soldi R, Bagala C, Graziani I, Landriscina M, Tarantini F, Duarte M, Bellum S, Doherty H, Maciag TThe non-classical export routes: FGF1 and IL-1alpha point the way. J Cell Sci. 2003;116:4871–4881.[PubMed][Google Scholar]
13. Jaye M, Howk R, Burgess W, Ricca GA, Chiu IM, Ravera MW, O’Brien SJ, Modi WS, Maciag T, Drohan WNHuman endothelial cell growth factor: cloning, nucleotide sequence, and chromosome localization. Science. 1986;233:541–545.[PubMed][Google Scholar]
14. Jackson A, Friedman S, Zhan X, Engleka KA, Forough R, Maciag THeat shock induces the release of fibroblast growth factor 1 from NIH 3T3 cells. Proc Natl Acad Sci U S A. 1992;89:10691–10695.[Google Scholar]
15. Misumi Y, Miki K, Takatsuki A, Tamura G, Ikehara YNovel blockade by brefeldin A of intracellular transport of secretory proteins in cultured rat hepatocytes. J Biol Chem. 1986;261:11398–11403.[PubMed][Google Scholar]
16. Prudovsky I, Bagala C, Tarantini F, Mandinova A, Soldi R, Bellum S, Maciag TThe intracellular translocation of the components of the fibroblast growth factor 1 release complex precedes their assembly prior to export. J Cell Biol. 2002;158:201–208.[Google Scholar]
17. Carreira C Mouta, Landriscina M, Bellum S, Prudovsky I, Maciag TThe comparative release of FGF1 by hypoxia and temperature stress. Growth Factors. 2001;18:277–285.[PubMed][Google Scholar]
18. Shin JT, Opalenik SR, Wehby JN, Mahesh VK, Jackson A, Tarantini F, Maciag T, Thompson JASerum-starvation induces the extracellular appearance of FGF-1. Biochim Biophys Acta. 1996;1312:27–38.[PubMed][Google Scholar]
19. Ananyeva NM, Tijurmin AV, Berliner JA, Chisolm GM, Liau G, Winkles JA, Haudenschild CCOxidized LDL mediates the release of fibroblast growth factor-1. Arterioscler Thromb Vasc Biol. 1997;17:445–453.[PubMed][Google Scholar]
20. Landriscina M, Bagala C, Mandinova A, Soldi R, Micucci I, Bellum S, Prudovsky I, Maciag TCopper induces the assembly of a multiprotein aggregate implicated in the release of fibroblast growth factor 1 in response to stress. J Biol Chem. 2001;276:25549–25557.[PubMed][Google Scholar]
21. Landriscina M, Soldi R, Bagala C, Micucci I, Bellum S, Tarantini F, Prudovsky I, Maciag TS100A13 participates in the release of fibroblast growth factor 1 in response to heat shock in vitro. J Biol Chem. 2001;276:22544–22552.[PubMed][Google Scholar]
22. LaVallee TM, Tarantini F, Gamble S, Carreira CM, Jackson A, Maciag TSynaptotagmin-1 is required for fibroblast growth factor-1 release. J Biol Chem. 1998;273:22217–22223.[PubMed][Google Scholar]
23. Yoshihara M, Montana ESThe synaptotagmins: calcium sensors for vesicular trafficking. Neuroscientist. 2004;10:566–574.[PubMed][Google Scholar]
24. Bagala C, Kolev V, Mandinova A, Soldi R, Mouta C, Graziani I, Prudovsky I, Maciag TThe alternative translation of synaptotagmin 1 mediates the non-classical release of FGF1. Biochem Biophys Res Commun. 2003;310:1041–1047.[PubMed][Google Scholar]
25. Tarantini F, Gamble S, Jackson A, Maciag TThe cysteine residue responsible for the release of fibroblast growth factor-1 residues in a domain independent of the domain for phosphatidylserine binding. J Biol Chem. 1995;270:29039–29042.[PubMed][Google Scholar]
26. Bai J, Chapman ERThe C2 domains of synaptotagmin--partners in exocytosis. Trends Biochem Sci. 2004;29:143–151.[PubMed][Google Scholar]
27. Rescher U, Gerke VAnnexins--unique membrane binding proteins with diverse functions. J Cell Sci. 2004;117:2631–2639.[PubMed][Google Scholar]
28. Nacken W, Sorg C, Kerkhoff CThe myeloid expressed EF-hand proteins display a diverse pattern of lipid raft association. FEBS Lett. 2004;572:289–293.[PubMed][Google Scholar]
29. Mach H, Middaugh CRInteraction of partially structured states of acidic fibroblast growth factor with phospholipid membranes. Biochemistry. 1995;34:9913–9920.[PubMed][Google Scholar]
30. Doyle AW, Fick J, Himmelhaus M, Eck W, Graziani I, Prudovsky I, Grunze M, Maciag T, Neivandt DProtein deformation of lipid hybrid bilayer membranes studied by Sum Frequency Generation Vibrational Spectroscopy (SFS) Langmuir. 2004;20:8961–8965.[PubMed][Google Scholar]
31. Copeland RA, Ji H, Halfpenny AJ, Williams RW, Thompson KC, Herber WK, Thomas KA, Bruner MW, Ryan JA, Marquis-Omer D, et al The structure of human acidic fibroblast growth factor and its interaction with heparin. Arch Biochem Biophys. 1991;289:53–61.[PubMed][Google Scholar]
32. Dabora JM, Sanyal G, Middaugh CREffect of polyanions on the refolding of human acidic fibroblast growth factor. J Biol Chem. 1991;266:23637–23640.[PubMed][Google Scholar]
33. Bychkova VE, Pain RH, Ptitsyn OBThe ‘molten globule’ state is involved in the translocation of proteins across membranes? FEBS Lett. 1988;238:231–234.[PubMed][Google Scholar]
34. Tarantini F, LaVallee T, Jackson A, Gamble S, Carreira C Mouta, Garfinkel S, Burgess WH, Maciag TThe extravesicular domain of synaptotagmin-1 is released with the latent fibroblast growth factor-1 homodimer in response to heat shock. J Biol Chem. 1998;273:22209–22216.[PubMed][Google Scholar]
35. Engleka KA, Maciag TInactivation of human fibroblast growth factor-1 (FGF-1) activity by interaction with copper ions involves FGF-1 dimer formation induced by copper-catalyzed oxidation. J Biol Chem. 1992;267:11307–11315.[PubMed][Google Scholar]
36. Mandinova A, Soldi R, Graziani I, Bagala C, Bellum S, Landriscina M, Tarantini F, Prudovsky I, Maciag TS100A13 mediates the copper-dependent stress-induced release of IL-1{alpha} from both human U937 and murine NIH 3T3 cells. J Cell Sci. 2003;116:2687–2696.[PubMed][Google Scholar]
37. Matsuzaki K, Murase O, Tokuda H, Funakoshi S, Fujii N, Miyajima KOrientational and aggregational states of magainin 2 in phospholipid bilayers. Biochemistry. 1994;33:3342–3349.[PubMed][Google Scholar]
38. Kida Y, Sakaguchi M, Fukuda M, Mikoshiba K, Mihara KAmino acid residues before the hydrophobic region which are critical for membrane translocation of the N-terminal domain of synaptotagmin II. FEBS Lett. 2001;507:341–345.[PubMed][Google Scholar]
39. Bai J, Tucker WC, Chapman ERPIP2 increases the speed of response of synaptotagmin and steers its membrane-penetration activity toward the plasma membrane. Nat Struct Mol Biol. 2004;11:36–44.[PubMed][Google Scholar]
40. McLaughlin S, Hangyas-Mihalyne G, Zaitseva I, Golebiewska UReversible - through calmodulin - electrostatic interactions between basic residues on proteins and acidic lipids in the plasma membrane. Biochem Soc Symp. 2005:189–198.[PubMed][Google Scholar]
41. Momchilova-Pankova AB, Markovska TT, Koumanov KSAcyl-CoA synthetase activity depends on the phospholipid composition of rat liver plasma membranes. J Lipid Mediat Cell Signal. 1995;11:13–23.[PubMed][Google Scholar]
42. Schroeder F, Fontaine RN, Feller DJ, Weston KGDrug-induced surface membrane phospholipid composition in murine fibroblasts. Biochim Biophys Acta. 1981;643:76–88.[PubMed][Google Scholar]
43. Kuypers FA, de Jong KThe role of phosphatidylserine in recognition and removal of erythrocytes. Cell Mol Biol (Noisy-le-grand) 2004;50:147–158.[PubMed][Google Scholar]
44. Kagan VE, Borisenko GG, Serinkan BF, Tyurina YY, Tyurin VA, Jiang J, Liu SX, Shvedova AA, Fabisiak JP, Uthaisang W, Fadeel BAppetizing rancidity of apoptotic cells for macrophages: oxidation, externalization, and recognition of phosphatidylserine. Am J Physiol Lung Cell Mol Physiol. 2003;285:L1–17.[PubMed][Google Scholar]
45. Donato RIntracellular and extracellular roles of S100 proteins. Microsc Res Tech. 2003;60:540–551.[PubMed][Google Scholar]
46. Holz RW, Hlubek MD, Sorensen SD, Fisher SK, Balla T, Ozaki S, Prestwich GD, Stuenkel EL, Bittner MAA pleckstrin homology domain specific for phosphatidylinositol 4, 5-bisphosphate (PtdIns-4,5-P2) and fused to green fluorescent protein identifies plasma membrane PtdIns-4,5-P2 as being important in exocytosis. J Biol Chem. 2000;275:17878–17885.[PubMed][Google Scholar]