SYNAPTOTAGMIN-1 IS REQUIRED FOR FIBROBLAST GROWTH-FACTOR-I RELEASE

By using p65 synaptotagmin-1 and fibroblast growth factor (FGF)-1:beta -galactosidase (beta-gal) NIH 3T3 cell cotransfectants, we demonstrate that a proteolytic fragment consisting of the extravesicular domain o f synaptotagmin-1 is released into the extracellular compartment in re sponse to temperature stress with similar kinetics and pharmacological properties as FGF-1:beta-gal, Using a deletion mutant that lacks 95 a mino acids from the extravesicular domain of synaptotagmin-1, neither synaptotagmin-1 nor FGF-1:beta-gal are able to access the stress-induc ed release pathway. Furthermore, the p40 extravesicular fragment of sy naptotagmin-1 is constitutively released in p40 synaptotagmin-1 NIH 3T 3 cell transfectants, and this release is potentiated when the cells a re subjected to temperature stress. These data demonstrate that the p4 0 fragment derived from synaptotagmin-1 is able to utilize the FGF-1 n on-classical exocytotic pathway and that the release of FGF-1 is depen dent on synaptotagmin-1.