Dynamics of Glucose-induced Membrane Recruitment of Protein Kinase C βII in Living Pancreatic Islet β-Cells

Pinton, Paolo; Tsuboi, Takashi; Ainscow, Edward; Pozzan, Tullio; Meneghesso, Gaudenzio; Rutter, Guy A.

doi:10.1074/jbc.m204478200

Cited by 91 publications

(80 citation statements)

References 66 publications

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“…Some of the difficulties to define the role of PKC in insulin secretion may be due to the enzyme being transiently activated during the oscillatory PLC activity. Consistent with this idea, coordinated oscillations of [Ca 2+ ] i and membrane translocation of PKCα, -βII and -ε have been observed in both clonal and primary β-cells (Pinton et al, 2002;Zhang et al, 2004;Suzuki et al, 2006).…”

Section: Pip 2 and Signalling Via Phospholipase Csupporting

confidence: 61%

Oscillatory control of insulin secretion

Tengholm

Gylfe

2009

Molecular and Cellular Endocrinology

162

169

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Pulsatile insulin secretionSince insulin is the only blood glucose-lowering hormone, its secretion is essential for glucose homeostasis, and disturbances are associated with glucose intolerance and diabetes.Glucose is the major stimulus for insulin release but secretion is enhanced also by other nutrients and is under stimulatory and inhibitory control by hormones and neurotransmitters.Although the external factors are essential determinants of insulin secretion, there are also input-independent variations in hormone release. Regular oscillations of the circulating insulin concentrations in normal subjects consequently occur without accompanying changes

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Section: Pip 2 and Signalling Via Phospholipase Csupporting

confidence: 61%

Oscillatory control of insulin secretion

Tengholm

Gylfe

2009

Molecular and Cellular Endocrinology

162

169

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“…A recent work reported the translocation of the PKC-␤II isoform to the plasma membrane and intracellular organelles, suggested to be mature insulin granules, in response to glucose (20). Although that report eloquently demonstrates the motion of the ␤II isoform in living cells, the functional significance of such motion (potential targets) remains to be addressed.…”

Section: Resultsmentioning

confidence: 99%

Rapid Association of Protein Kinase C-ϵ with Insulin Granules Is Essential for Insulin Exocytosis

Méndez

Leibiger

et al. 2003

Journal of Biological Chemistry

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Glucose-dependent exocytosis of insulin requires activation of protein kinase C (PKC). However, because of the great variety of isoforms and their ubiquitous distribution within the ␤-cell, it is difficult to predict the importance of a particular isoform and its mode of action. Previous data revealed that two PKC isoforms (␣ and ⑀) translocate to membranes in response to glucose (Zaitzev, S. V., Efendic, S., Arkhammar, P., Bertorello, A. M., and Berggren, P. O. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 9712-9716). Using confocal microscopy, we have now established that in response to glucose, PKC-⑀ but not PKC-␣ associates with insulin granules and that green fluorescent protein-tagged PKC-⑀ changes its distribution within the cell periphery upon stimulation of ␤-cells with glucose. Definite evidence of PKC-⑀ requirement during insulin granule exocytosis was obtained by using a dominant negative mutant of this isoform. The presence of this mutant abolished glucose-induced insulin secretion, whereas transient expression of the wildtype PKC-⑀ led to a significant increase in insulin exocytosis. These results suggest that association of PKC-⑀ with insulin granule membranes represents an important component of the secretory network because it is essential for insulin exocytosis in response to glucose.In pancreatic ␤-cells, glucose metabolism generates a great variety of intracellular signals that in concert promote insulin exocytosis (for review see Refs. 1 and 2). There are other insulin secretagogues; however, their mode of action occasionally involves the regulation of signaling molecules that are different from the ones regulated in response to glucose. Among those signals, particular attention has been focused on the role of protein kinase C (PKC) 1 because it is known that protein phosphorylation/dephosphorylation can rapidly affect the function of a given protein or signaling molecule in response to a given agonist (3, 4). Definite proof of the role that PKC may have in the process of insulin exocytosis has been difficult to obtain, primarily because of the great diversity of PKC isoforms, the lack of specific inhibitors, and the use of different experimental designs and cell models to study their functions (for review see Ref. 5).Previous attempts to establish the identity of the PKC isoforms that are responsive to glucose in pancreatic ␤-cells, although complex, indicated that the ␣ and ⑀ isoforms are likely candidates (6, 7). Moreover, cell fractionation assays of intact islets exposed to high glucose confirm that both PKC-␣ and PKC-⑀ isoforms indeed translocate to membranes, an event that was even fast enough to coincide with the initial phase of insulin secretion (8). Using antibodies against specific PKC isoforms and selective anchoring peptides that block their activation, it was possible to assess the role of different isoforms during glucose-stimulated insulin secretion (9). Although the results of that study (9) further supported a pivotal role of PKC-␣ and PKC-⑀ by their translocation to the plas...

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“…Therefore, the subplasmamembranous domains have been one of the major targets of GECIs, and several types of GECIs have been localized to the plasma membrane by fusion with plasma membrane-anchoring motifs, such as myristoylation, palmitoylation, or farnesylation tags (18,61), or with plasma membrane-localized transporters (62,63). GEGIs fused with synaptic proteins, such as synaptosome-associated protein of 25 kDa (SNAP25), synaptophysin, and synaptobrevin, have been also used to detect microdomain Ca 2þ signals in the synapse (18,64). Recently, optical recordings of channel activities on the plasma membrane have been reported, whereby GECIs were localized within close proximity of Ca 2þ channels by a direct fusion with the channel proteins.…”

Section: Subplasmamembranementioning

confidence: 99%

Genetically Encoded Fluorescent Indicators for Organellar Calcium Imaging

Suzuki

Kanemaru

Iino

2016

Biophysical Journal

112

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Optical Ca 2þ indicators are powerful tools for investigating intracellular Ca 2þ signals in living cells. Although a variety of Ca 2þ indicators have been developed, deciphering the physiological functions and spatiotemporal dynamics of Ca 2þ in intracellular organelles remains challenging. Genetically encoded Ca 2þ indicators (GECIs) using fluorescent proteins are promising tools for organellar Ca 2þ imaging, and much effort has been devoted to their development. In this review, we first discuss the key points of organellar Ca 2þ imaging and summarize the requirements for optimal organellar Ca 2þ indicators. Then, we highlight some of the recent advances in the engineering of fluorescent GECIs targeted to specific organelles. Finally, we discuss the limitations of currently available GECIs and the requirements for advancing the research on intraorganellar Ca 2þ signaling.

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Dynamics of Glucose-induced Membrane Recruitment of Protein Kinase C βII in Living Pancreatic Islet β-Cells

Cited by 91 publications

References 66 publications

Oscillatory control of insulin secretion

Oscillatory control of insulin secretion

Rapid Association of Protein Kinase C-ϵ with Insulin Granules Is Essential for Insulin Exocytosis

Genetically Encoded Fluorescent Indicators for Organellar Calcium Imaging

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