Proteome of the insulin-secreting Min6 cell porosome complex: Involvement of Hsp90 in its assembly and function

Rajagopal, Amulya; Kulkarni, Sanjana; Lewis, Kenneth T.; Maarouf, A.; Kelly, Christopher V.; Taatjes, Douglas J.; Jena, Bhanu P.

doi:10.1016/j.jprot.2014.11.010

Cited by 14 publications

(13 citation statements)

References 63 publications

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“…Hsp90β was shown to participate in the biogenesis of K ATP channels which are one of the basic components involved in insulin secretion . In MIN6 mouse β‐cells, Hsp90 contributes to the assembly and function of porosomes, which are plasma membrane‐located secretory portals involved in the regulated release of intravesicular contents from cells . There are also indications that Hsp90 is involved in the recognition and degradation of non‐native proteins on the plasma membrane .…”

Section: Discussionmentioning

confidence: 99%

Stearate‐Induced Apoptosis in Human Pancreatic β‐Cells is Associated with Changes in Membrane Protein Expression and These Changes are Inhibited by Oleate

Němcová‐Fürstová

Balušíková

Halada

et al. 2019

Proteomics Clinical Apps

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Purpose: Lipotoxicity is implicated in type 2 diabetes pathogenesis. Its molecular mechanisms are not completely understood. The aim of this study is to identify new suspect proteins involved in pancreatic ␤-cell death induction by saturated fatty acids and its inhibition by unsaturated fatty acids. Experimental design: Employing 2DE analysis and subsequent western blot confirmation, the differences in membrane/membrane-associated protein expression in human ␤-cell line NES2Y are assessed during cell death induction by stearate and its inhibition by oleate. Results: Induction of apoptosis by stearate is associated with significantly increased levels of Hsp90␤, peroxiredoxin-1, and 14-3-3␥ in the membrane fraction of NES2Y cells and significantly decreased levels of annexin A2, annexin A4, and reticulocalbin-2. All these changes are significantly inhibited by oleate co-application. No expression changes are detected after application of stearate together with oleate. Furthermore, the expression of reticulocalbin-2 is significantly decreased after stearate application also in the whole cell lysate. Conclusions and clinical relevance: Several membrane-associated proteins that could be related to pro-and anti-apoptotic signaling initiated by fatty acids in human pancreatic ␤-cells are identified. As far as we know, annexin A4, reticulocalbin-2, and 14-3-3␥ represent novel molecules related to the effect of fatty acids on ␤-cell viability.

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Section: Discussionmentioning

confidence: 99%

Stearate‐Induced Apoptosis in Human Pancreatic β‐Cells is Associated with Changes in Membrane Protein Expression and These Changes are Inhibited by Oleate

Němcová‐Fürstová

Balušíková

Halada

et al. 2019

Proteomics Clinical Apps

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“…ATP triggers the opening of voltage-gated calcium channels via inhibition of ATP-sensitive potassium channels in plasma membrane. The Ca 2+ influx then stimulates exocytosis of insulin from the secretory vesicles that fuse with the plasma membrane, at the level of a complex protein structure known as the porosome (Rorsman & Renström, 2003; Rajagopala et al, 2015). At this level, among the many factors involved in vesicle fusion, SNARE proteins (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) play a critical role.…”

Section: Discussionmentioning

confidence: 99%

Ultrastructural Analysis of In Vivo Hypoglycemiant Effect of Two Polyoxometalates in Rats with Streptozotocin-Induced Diabetes

et al. 2015

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Two polyoxometalates (POMs), synthesized through a self-assembling method, were used in the treatment of streptozotocin (STZ)-induced diabetic rats. One of these nanocompounds [tris(vanadyl)-substituted tungsto-antimonate(III)-anions—POM1] was previously described in the literature, whereas the second [tris-butyltin-21-tungsto-9-antimonate(III)-anions—POM2], was prepared by us based on our original formula. In rats with STZ-induced diabetes treated with POMs (up to a cumulative dose of 4 mg/kg bodyweight at the end of the treatments), statistically significant reduced levels of blood glucose were measured after 3 weeks, as compared with the diabetic control groups (DCGs). Ultrastructural analysis of pancreatic β-cells (including the mean diameter of secretory vesicles and of their insulin granules) in the treated diabetic rats proved the POMs contribute to limitation of cellular degeneration triggered by STZ, as well as to the presence of increased amounts of insulin-containing vesicles as compared with the DCG. The two POMs also showed hepatoprotective properties when ultrastructural aspects of hepatocytes in the experimental groups of rats were studied. Based on our in vivo studies, we concluded that the two POMs tested achieved hypoglycemiant effects by preventing STZ-triggered apoptosis of pancreatic β-cells and stimulation of insulin synthesis.

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“…The presence and morphology of these secretory portals were further confirmed using electron microscopy (EM), 6,7 and their presence was established in all secretory cells examined including neurons, [7][8][9][10][11][12][13][14][15][16][17][18][19][20] initially by our group [7][8][9][10][11][12][13][14][15][16][17][18][19][20] and subsequently by other laboratories. [21][22][23][24][25][26][27][28][29][30] The function of the porosome as a universal secretory portal, its chemical composition, [7][8][9]13,19,20 and its functional and structural reconstitution, 6,8 has greatly advanced our understanding of this vital cellular organelle. Furthermore in neurons, the native porosome with docked synapt...…”

Section: Introductionmentioning

confidence: 94%

The neuronal porosome complex in health and disease

Naik

Lewis

Jena

2015

Exp Biol Med (Maywood)

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Cup-shaped secretory portals at the cell plasma membrane called porosomes mediate the precision release of intravesicular material from cells. Membrane-bound secretory vesicles transiently dock and fuse at the base of porosomes facing the cytosol to expel pressurized intravesicular contents from the cell during secretion. The structure, isolation, composition, and functional reconstitution of the neuronal porosome complex have greatly progressed, providing a molecular understanding of its function in health and disease. Neuronal porosomes are 15 nm cup-shaped lipoprotein structures composed of nearly 40 proteins, compared to the 120 nm nuclear pore complex composed of >500 protein molecules. Membrane proteins compose the porosome complex, making it practically impossible to solve its atomic structure. However, atomic force microscopy and small-angle X-ray solution scattering studies have provided three-dimensional structural details of the native neuronal porosome at sub-nanometer resolution, providing insights into the molecular mechanism of its function. The participation of several porosome proteins previously implicated in neurotransmission and neurological disorders, further attest to the crosstalk between porosome proteins and their coordinated involvement in release of neurotransmitter at the synapse.

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Proteome of the insulin-secreting Min6 cell porosome complex: Involvement of Hsp90 in its assembly and function

Cited by 14 publications

References 63 publications

Stearate‐Induced Apoptosis in Human Pancreatic β‐Cells is Associated with Changes in Membrane Protein Expression and These Changes are Inhibited by Oleate

Stearate‐Induced Apoptosis in Human Pancreatic β‐Cells is Associated with Changes in Membrane Protein Expression and These Changes are Inhibited by Oleate

Ultrastructural Analysis of In Vivo Hypoglycemiant Effect of Two Polyoxometalates in Rats with Streptozotocin-Induced Diabetes

The neuronal porosome complex in health and disease

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