TY - JOUR
T1 - Syntaxin 4 and Synip (syntaxin 4 interacting protein) regulate insulin secretion in the pancreatic β HC-9 cell
AU - Saito, Tsugumichi
AU - Okada, Shuichi
AU - Yamada, Eijiro
AU - Ohshima, Kihachi
AU - Shimizu, Hiroyuki
AU - Shimomura, Kenju
AU - Sato, Minoru
AU - Pessin, Jeffrey E.
AU - Mori, Masatomo
PY - 2003/9/19
Y1 - 2003/9/19
N2 - Although syntaxin 1 is generally thought to function as the primary target-N-ethylmaleimide-sensitive factor attachment protein receptor required for pancreatic β cell insulin secretion, we have observed that overexpression of a dominant-interfering syntaxin 4 mutant (syntaxin 4/ΔTM) attenuated glucose-stimulated insulin secretion in βHC-9 cells. Furthermore, these cells express the selective syntaxin 4-binding protein Synip (syntaxin 4 interacting protein), and Synip was specifically co-immunoprecipitated with syntaxin 4 but not syntaxin 1. Overexpression of the full-length Synip protein (Synip/wild type) inhibited VAMP2 association with syntaxin 4 and decreased glucose-stimulated insulin secretion. This did not occur with a Synip mutant (Synip/ΔEF) that was incapable of binding syntaxin 4. Consistent with a functional role of syntaxin 4 in this process, expression of syntaxin 4/ΔTM also inhibited glucose-stimulated insulin secretion. Furthermore, analysis of first and second phase insulin secretion demonstrated that syntaxin 4/ΔTM mainly suppressed the second phase of insulin secretion. In contrast, overexpression of Synip resulted in an inhibition of both the first and second phase of glucose-stimulated insulin secretion. These data demonstrate that syntaxin 4 plays a functional role on insulin release and granule fusion in β cells and that this process is regulated by the syntaxin 4-specific binding protein Synip.
AB - Although syntaxin 1 is generally thought to function as the primary target-N-ethylmaleimide-sensitive factor attachment protein receptor required for pancreatic β cell insulin secretion, we have observed that overexpression of a dominant-interfering syntaxin 4 mutant (syntaxin 4/ΔTM) attenuated glucose-stimulated insulin secretion in βHC-9 cells. Furthermore, these cells express the selective syntaxin 4-binding protein Synip (syntaxin 4 interacting protein), and Synip was specifically co-immunoprecipitated with syntaxin 4 but not syntaxin 1. Overexpression of the full-length Synip protein (Synip/wild type) inhibited VAMP2 association with syntaxin 4 and decreased glucose-stimulated insulin secretion. This did not occur with a Synip mutant (Synip/ΔEF) that was incapable of binding syntaxin 4. Consistent with a functional role of syntaxin 4 in this process, expression of syntaxin 4/ΔTM also inhibited glucose-stimulated insulin secretion. Furthermore, analysis of first and second phase insulin secretion demonstrated that syntaxin 4/ΔTM mainly suppressed the second phase of insulin secretion. In contrast, overexpression of Synip resulted in an inhibition of both the first and second phase of glucose-stimulated insulin secretion. These data demonstrate that syntaxin 4 plays a functional role on insulin release and granule fusion in β cells and that this process is regulated by the syntaxin 4-specific binding protein Synip.
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U2 - 10.1074/jbc.M305114200
DO - 10.1074/jbc.M305114200
M3 - Article
C2 - 12855681
AN - SCOPUS:0141814988
SN - 0021-9258
VL - 278
SP - 36718
EP - 36725
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 38
ER -