Non-functional role of syntaxin 2 in insulin exocytosis by pancreatic β cells

Nagamatsu, Shinya; Sawa, Hiroki; Nakamichi, Yoko; Kondo, Yoshinori; Matsushima, Satsuki; Watanabe, Takashi

doi:10.1002/(sici)1099-0844(199712)15:4<237::aid-cbf746>3.0.co;2-u

Cited by 10 publications

(7 citation statements)

References 26 publications

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“…Other reports include synaptotagmin III (59,60), rabphilin and rab3A (61), and cellubrevin (62). Evidence is available that syntaxin 1 but not syntaxin 2 is involved in ␤-cell exocytosis (63)(64)(65). VAMP-2 and cellubrevin are required for Ca 2ϩ -stimulated exocytosis but may not be involved in GTP-stimulated exocytosis (34).…”

Section: Exocytosis In the Pancreatic ␤-Cellmentioning

confidence: 99%

Triggering and Augmentation Mechanisms, Granule Pools, and Biphasic Insulin Secretion

et al. 2002

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The insulin secretory response by pancreatic ␤-cells to an acute "square wave" stimulation by glucose is characterized by a first phase that occurs promptly after exposure to glucose, followed by a decrease to a nadir, and a prolonged second phase. The first phase of release is due to the ATP-sensitive K ؉ (K ATP ) channel-dependent (triggering) pathway that increases [Ca 2؉ ] i and has been thought to discharge the granules from a "readily releasable pool." It follows that the second phase entails the preparation of granules for release, perhaps including translocation and priming for fusion competency before exocytosis. The pathways responsible for the second phase include the K ATP channel-dependent pathway because of the need for elevated [Ca 2؉ ] i and additional signals from K ATP channel-independent pathways. The mechanisms underlying these additional signals are unknown. Current hypotheses include increased cytosolic long-chain acyl-CoA, the pyruvatemalate shuttle, glutamate export from mitochondria, and an increased ATP/ADP ratio. In mouse islets, the ␤-cell contains some 13,000 granules, of which ϳ100 are in a "readily releasable" pool. Rates of granule release are slow, e.g., one every 3 s, even at the peak of the first phase of glucose-stimulated release. As both phases of glucose-stimulated insulin secretion can be enhanced by agents such as glucagon-like peptide 1, which increases cyclic AMP levels and protein kinase A activity, or acetylcholine, which increases diacylglycerol levels and protein kinase C activity, a single "readily releasable pool" hypothesis is an inadequate explanation for insulin secretion. Multiple pools available for rapid release or rapid conversion of granules to a rapidly releasable state are required. Diabetes 51 (Suppl. 1):S83-S90, 2002

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Section: Exocytosis In the Pancreatic ␤-Cellmentioning

confidence: 99%

Triggering and Augmentation Mechanisms, Granule Pools, and Biphasic Insulin Secretion

et al. 2002

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“…The gene that encodes EPM also encodes syntaxin-2, a protein that has been shown to function during targeting/ fusion of intracellular vesicles with the plasma membrane (Bennett et al, 1993;Pelham, 1993). Although syntaxins have been shown to act at the cytoplasmic face of membranes (Brose, 1993;Pelham, 1993;Rothman, 1994;Wheeler et al, 1996;Jagadish et al, 1997), the subcellular localization of syntaxins can be modulated through various mechanisms (Hui et al, 1997;Jagadish et al, 1997;Rodger et al, 1998;Quiñones et al, 1999), and syntaxins have been found at the cell surface at least transiently (Hirai et al, 1993(Hirai et al, , 1998Smirnova et al, 1993a,b;Butt et al, 1996;Nagamatsu et al, 1997;Guo et al, 1998). Evidently, these complex and versatile proteins can perform multiple functions, and it will be a considerable challenge to discover how these diverse roles are related.…”

Section: Epm Is a Member Of The Syntaxin Familymentioning

confidence: 99%

Epimorphin Mediates Mammary Luminal Morphogenesis through Control of C/EBPβ

Hirai

Radisky

Boudreau

et al. 2001

The Journal of Cell Biology

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We have shown previously that epimorphin (EPM), a protein expressed on the surface of myoepithelial and fibroblast cells of the mammary gland, acts as a multifunctional morphogen of mammary epithelial cells. Here, we present the molecular mechanism by which EPM mediates luminal morphogenesis. Treatment of cells with EPM to induce lumen formation greatly increases the overall expression of transcription factor CCAAT/enhancer binding protein (C/EBP)β and alters the relative expression of its two principal isoforms, LIP and LAP. These alterations were shown to be essential for the morphogenetic activities, since constitutive expression of LIP was sufficient to produce lumen formation, whereas constitutive expression of LAP blocked EPM-mediated luminal morphogenesis. Furthermore, in a transgenic mouse model in which EPM expression was expressed in an apolar fashion on the surface of mammary epithelial cells, we found increased expression of C/EBPβ, increased relative expression of LIP to LAP, and enlarged ductal lumina. Together, our studies demonstrate a role for EPM in luminal morphogenesis through control of C/EBPβ expression.

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“…Previous studies have shown that t-SNARE family proteins are expressed in islets of Langerhans and regulate insulin release (Jacobsson et al 1994;Wheeler et al 1996;Nagamatsu et al 1999). However, the expression of EPM/syntaxin 2 in islets was found to be low and the function was unrelated to the insulin exocytosis pathway (Nagamatsu et al 1997). Our data demonstrate that EPM protein is expressed in the micro blood vessels and mesenchymal cells inside islets, which therefore suggests that it may not play a role in insulin exocytosis, though it could play a role in islet morphogenesis (Lammert et al 2001;Konstantinova & Lammert 2004).…”

Section: Discussionmentioning

confidence: 96%

“…1999). However, the expression of EPM/syntaxin 2 in islets was found to be low and the function was unrelated to the insulin exocytosis pathway (Nagamatsu et al . 1997).…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal epimorphin is important for pancreatic duct morphogenesis

et al. 2006

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Epithelial-mesenchymal interactions are crucial for the proper development of many organs, including the pancreas. Within the pancreas, the ducts are thought to harbor stem/progenitor cells, and possibly to give rise to pancreatic ductal carcinoma. Little is known about the mechanism of formation of pancreatic ducts in the embryo. Pancreatic mesenchyme contains numerous soluble factors which help to sustain the growth and differentiation of exocrine and endocrine structures. Here, we report that one such morphoregulatory mesenchymal protein, epimorphin, plays an important role during pancreatic ductal proliferation and differentiation. We found that epimorphin is expressed in pancreatic mesenchyme during early stages of development, and at mesenchymal-epithelial interfaces surrounding the ducts at later stages. Strong upregulation of epimorphin expression was seen during in vitro pancreatic duct differentiation. Similarly, in vitro pancreatic duct formation was inhibited by a neutralizing antibody against epimorphin, whereas addition of recombinant epimorphin partially rescued duct formation. Together, our study demonstrates the role of epimorphin in pancreatic ductal morphogenesis.

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Non-functional role of syntaxin 2 in insulin exocytosis by pancreatic β cells

Cited by 10 publications

References 26 publications

Triggering and Augmentation Mechanisms, Granule Pools, and Biphasic Insulin Secretion

Triggering and Augmentation Mechanisms, Granule Pools, and Biphasic Insulin Secretion

Epimorphin Mediates Mammary Luminal Morphogenesis through Control of C/EBPβ

Mesenchymal epimorphin is important for pancreatic duct morphogenesis

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