Synaptotagmin-1 is required for fibroblast growth factor-1 release.
By using p65 synaptotagmin-1 and fibroblast growth factor (FGF)-1:beta-galactosidase (beta-gal) NIH 3T3 cell co-transfectants, we demonstrate that a proteolytic fragment consisting of the extravesicular domain of synaptotagmin-1 is released into the extracellular compartment in response to temperature stress with similar kinetics and pharmacological properties as FGF-1:beta-gal. Using a deletion mutant that lacks 95 amino acids from the extravesicular domain of synaptotagmin-1, neither synaptotagmin-1 nor FGF-1:beta-gal are able to access the stress-induced release pathway. Furthermore, the p40 extravesicular fragment of synaptotagmin-1 is constitutively released in p40 synaptotagmin-1 NIH 3T3 cell transfectants, and this release is potentiated when the cells are subjected to temperature stress. These data demonstrate that the p40 fragment derived from synaptotagmin-1 is able to utilize the FGF-1 non-classical exocytotic pathway and that the release of FGF-1 is dependent on synaptotagmin-1.
Department of Molecular Biology, Holland Laboratory, American Red Cross, Rockville, Maryland 20855, USA.
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LaVallee
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Tarantini
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Gamble
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Mouta Carreira
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Jackson
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Maciag
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002135:Calcium-Binding Proteins; D017931:DNA Primers; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D018869:Heat-Shock Response; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051381:Rats; D050863:Synaptotagmin I; D050857:Synaptotagmins; D001616:beta-Galactosidase / Q000235:genetics
D002135:Calcium-Binding Proteins; D017931:DNA Primers; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D050863:Synaptotagmin I; C494311:Syt1 protein, mouse; C494312:Syt1 protein, rat; D050857:Synaptotagmins; D005346:Fibroblast Growth Factors; D001616:beta-Galactosidase