Synip

Jiang, Min; Okada, Shuichi; Kanzaki, Makoto; Elmendorf, Jeffrey S.; Coker, Kenneth J.; Ceresa, Brian P.; Syu, Li-Jyun; Noda, Yoichi; Saltiel, Alan R.; Pessin, Jeffrey E.

doi:10.1016/s1097-2765(01)80007-1

Cited by 172 publications

(65 citation statements)

References 52 publications

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“…Previously, we reported that Synip binding to syntaxin 4 competes for VAMP2 binding and is therefore mutually exclusive (18). As expected, overexpression of Synip completely prevented the association of VAMP2 with syntaxin 4 before and after glucose stimulation and inhibited glucose-stimulated insulin secretion.…”

Section: Discussionsupporting

confidence: 83%

“…As a control for syntaxin 4 and Synip specificity, we also expressed Synip/WT and examined its binding to syntaxin 1. As reported previously (18), the immunoprecipitation of Synip/WT resulted in the co-precipitation of syntaxin 4 but not syntaxin 1 (data not shown). Together, these data suggest that syntaxin 4 and Synip may both play functional roles in glucosestimulated insulin secretion.…”

Section: Synip Expression In ␤Hc-9supporting

confidence: 86%

“…Cells-Previously, we reported that Synip is expressed in muscle and adipose tissue (18). In comparison, Northern blot analysis of RNA from differentiated 3T3L1 adipocytes and ␤HC-9 cells demonstrated the presence of the major 7.5-kb Synip transcript (Fig.…”

Section: Synip Expression In ␤Hc-9mentioning

confidence: 77%

“…Materials-The FLAG M2 monoclonal antibody was obtained from Sigma, and syntaxin 4 sheep polyclonal and Synip rabbit polyclonal antibodies were prepared and affinity-purified as described previously (18,19). ECLϩplus Western blotting detection system and [␣-32 P]dCTP were purchased from Amersham Biosciences.…”

Section: Methodsmentioning

confidence: 99%

“…Following electroporation and stimulation, the cell medium was collected for analysis by an insulin radioimmunoassay. A total amount of cell protein was determined by extraction of the cells with a Nonidet P-40 lysis buffer and used to normalize for the amount of insulin release (18). All data are expressed as mean Ϯ S.D.…”

Section: Methodsmentioning

confidence: 99%

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Syntaxin 4 and Synip (Syntaxin 4 Interacting Protein) Regulate Insulin Secretion in the Pancreatic β HC-9 Cell

Saito

Okada

Yamada

et al. 2003

Journal of Biological Chemistry

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Although syntaxin 1 is generally thought to function as the primary target-N-ethylmaleimide-sensitive factor attachment protein receptor required for pancreatic ␤ cell insulin secretion, we have observed that overexpression of a dominant-interfering syntaxin 4 mutant (syntaxin 4/⌬TM) attenuated glucose-stimulated insulin secretion in ␤HC-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/ ⌬EF) that was incapable of binding syntaxin 4. Consistent with a functional role of syntaxin 4 in this process, expression of syntaxin 4/⌬TM also inhibited glucosestimulated insulin secretion. Furthermore, analysis of first and second phase insulin secretion demonstrated that syntaxin 4/⌬TM 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 ␤ cells and that this process is regulated by the syntaxin 4-specific binding protein Synip.It is well established that glucose-stimulated insulin secretion occurs through a complex metabolic network in which the increased flux of glucose in pancreatic ␤ cells elevates the intracellular ATP/ADP ratio (1-5). The increased ATP/ADP ratio results in the closure of the ATP-sensitive potassium channel (K ATP channels) and subsequent cellular depolarization (6, 7). In turn, depolarization causes the activation of the L-type voltage-dependent calcium channels that result in the influx of extracellular calcium. This increased intracellular calcium then serves as a trigger for the initial fusion of insulincontaining dense core granules with the plasma membrane (8, 9).Although the calcium trigger mechanism, trafficking, and fusion of insulin granules have not been fully elucidated, recent studies have suggested that the majority of granules that initially fuse with the plasma membrane are localized beneath the plasma membrane in a bound (docked) state (10 -12). This pool of insulin granules has been referred as the readily releasable pool, and it appears to account for the first phase of stimulusmediated insulin secretion (13). This initial release process requires the functional interactions of the t-SNARE 1 proteins, syntaxin 1 and SNAP25, with the v-SNARE protein, VAMP2. For example, the use of SNARE mutants or various SNARE protein-specific proteolytic toxins prevent regulated insulin secretion (14 -17). However, since these endotoxins do not proteolyze complexed SNARE proteins, it is thought that the plasma membrane-bound (docked) insulin granules first undergo a priming step (core SNARE complex...

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Section: Discussionsupporting

confidence: 83%

Section: Synip Expression In ␤Hc-9supporting

confidence: 86%

Section: Synip Expression In ␤Hc-9mentioning

confidence: 77%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Syntaxin 4 and Synip (Syntaxin 4 Interacting Protein) Regulate Insulin Secretion in the Pancreatic β HC-9 Cell

Saito

Okada

Yamada

et al. 2003

Journal of Biological Chemistry

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Cell-Surface Recognition of Biotinylated Membrane Proteins Requires Very Long Spacer Arms: An Example from Glucose-Transporter Probes

2001

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Glucose transporters (GLUTs) can be photoaffinity labelled by (diazirinetrifluoroethyl)benzoyl-substituted glucose derivatives and the adduct can be recognised, after detergent solubilisation of membranes, by using streptavidin-based detection systems. However, in intact cells recognition of photolabelled GLUTs by avidin and anti-biotin antibodies only occurs if the bridge between the photoreactive and the biotin moieties has a minimum of 60--70 spacer atoms. We show that a suitably long bridge can be synthesised with a combination of polyethylene glycol and tartarate groups and that introduction of these spacers generates hydrophilic products that can be cleaved with periodate. Introduction of the very long spacers does not appreciably reduce the affinity of interaction of the probes with the transport system.

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Spatial compartmentalization of signal transduction in insulin action

Baumann

Saltiel

2001

Bioessays

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Insulin resistance is thought to be the primary defect in the pathophysiology of type 2 diabetes. Thus, understanding the cellular mechanisms of insulin action may contribute significantly to developing new treatments for this disease. Although the effects of insulin on glucose and lipid metabolism are well documented, gaps remain in our understanding of the precise molecular mechanisms of signal transduction for the hormone. One potential clue to understanding the unique cellular effects of insulin may lie in the compartmentalization of signaling molecules and metabolic enzymes. We review this evidence, and speculate on how PI-3 kinase-independent and -dependent signaling pathways both diverge from the insulin receptor and converge at discrete targets to insure the specificity of insulin action.

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Synip

Cited by 172 publications

References 52 publications

Syntaxin 4 and Synip (Syntaxin 4 Interacting Protein) Regulate Insulin Secretion in the Pancreatic β HC-9 Cell

Syntaxin 4 and Synip (Syntaxin 4 Interacting Protein) Regulate Insulin Secretion in the Pancreatic β HC-9 Cell

Cell-Surface Recognition of Biotinylated Membrane Proteins Requires Very Long Spacer Arms: An Example from Glucose-Transporter Probes

Spatial compartmentalization of signal transduction in insulin action

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