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Role of the active zone protein, ELKS, in insulin secretion from pancreatic β-cells

BACKGROUND: Insulin is stored within large dense-core granules in pancreatic beta (β)-cells and is released by Ca(2+)-triggered exocytosis with increasing blood glucose levels. Polarized and targeted secretion of insulin from β-cells in pancreatic islets into the vasculature has been proposed; howev...

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Autores principales: Ohara-Imaizumi, Mica, Aoyagi, Kyota, Ohtsuka, Toshihisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768504/
https://www.ncbi.nlm.nih.gov/pubmed/31500835
http://dx.doi.org/10.1016/j.molmet.2019.06.017
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author Ohara-Imaizumi, Mica
Aoyagi, Kyota
Ohtsuka, Toshihisa
author_facet Ohara-Imaizumi, Mica
Aoyagi, Kyota
Ohtsuka, Toshihisa
author_sort Ohara-Imaizumi, Mica
collection PubMed
description BACKGROUND: Insulin is stored within large dense-core granules in pancreatic beta (β)-cells and is released by Ca(2+)-triggered exocytosis with increasing blood glucose levels. Polarized and targeted secretion of insulin from β-cells in pancreatic islets into the vasculature has been proposed; however, the mechanisms related to cellular and molecular localization remain largely unknown. Within nerve terminals, the Ca(2+)-dependent release of a polarized transmitter is limited to the active zone, a highly specialized area of the presynaptic membrane. Several active zone-specific proteins have been characterized; among them, the CAST/ELKS protein family members have the ability to form large protein complexes with other active zone proteins to control the structure and function of the active zone for tight regulation of neurotransmitter release. Notably, ELKS but not CAST is also expressed in β-cells, implying that ELKS may be involved in polarized insulin secretion from β-cells. SCOPE OF REVIEW: This review provides an overview of the current findings regarding the role(s) of ELKS and other active zone proteins in β-cells and focuses on the molecular mechanism underlying ELKS regulation within polarized insulin secretion from islets. MAJOR CONCLUSIONS: ELKS localizes at the vascular-facing plasma membrane of β-cells in mouse pancreatic islets. ELKS forms a potent insulin secretion complex with L-type voltage-dependent Ca(2+) channels on the vascular-facing plasma membrane of β-cells, enabling polarized Ca(2+) influx and first-phase insulin secretion from islets. This model provides novel insights into the functional polarity observed during insulin secretion from β-cells within islets at the molecular level. This active zone-like region formed by ELKS at the vascular side of the plasma membrane is essential for coordinating physiological insulin secretion and may be disrupted in diabetes.
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spelling pubmed-67685042019-10-07 Role of the active zone protein, ELKS, in insulin secretion from pancreatic β-cells Ohara-Imaizumi, Mica Aoyagi, Kyota Ohtsuka, Toshihisa Mol Metab Review BACKGROUND: Insulin is stored within large dense-core granules in pancreatic beta (β)-cells and is released by Ca(2+)-triggered exocytosis with increasing blood glucose levels. Polarized and targeted secretion of insulin from β-cells in pancreatic islets into the vasculature has been proposed; however, the mechanisms related to cellular and molecular localization remain largely unknown. Within nerve terminals, the Ca(2+)-dependent release of a polarized transmitter is limited to the active zone, a highly specialized area of the presynaptic membrane. Several active zone-specific proteins have been characterized; among them, the CAST/ELKS protein family members have the ability to form large protein complexes with other active zone proteins to control the structure and function of the active zone for tight regulation of neurotransmitter release. Notably, ELKS but not CAST is also expressed in β-cells, implying that ELKS may be involved in polarized insulin secretion from β-cells. SCOPE OF REVIEW: This review provides an overview of the current findings regarding the role(s) of ELKS and other active zone proteins in β-cells and focuses on the molecular mechanism underlying ELKS regulation within polarized insulin secretion from islets. MAJOR CONCLUSIONS: ELKS localizes at the vascular-facing plasma membrane of β-cells in mouse pancreatic islets. ELKS forms a potent insulin secretion complex with L-type voltage-dependent Ca(2+) channels on the vascular-facing plasma membrane of β-cells, enabling polarized Ca(2+) influx and first-phase insulin secretion from islets. This model provides novel insights into the functional polarity observed during insulin secretion from β-cells within islets at the molecular level. This active zone-like region formed by ELKS at the vascular side of the plasma membrane is essential for coordinating physiological insulin secretion and may be disrupted in diabetes. Elsevier 2019-09-06 /pmc/articles/PMC6768504/ /pubmed/31500835 http://dx.doi.org/10.1016/j.molmet.2019.06.017 Text en © 2019 Published by Elsevier GmbH. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Review
Ohara-Imaizumi, Mica
Aoyagi, Kyota
Ohtsuka, Toshihisa
Role of the active zone protein, ELKS, in insulin secretion from pancreatic β-cells
title Role of the active zone protein, ELKS, in insulin secretion from pancreatic β-cells
title_full Role of the active zone protein, ELKS, in insulin secretion from pancreatic β-cells
title_fullStr Role of the active zone protein, ELKS, in insulin secretion from pancreatic β-cells
title_full_unstemmed Role of the active zone protein, ELKS, in insulin secretion from pancreatic β-cells
title_short Role of the active zone protein, ELKS, in insulin secretion from pancreatic β-cells
title_sort role of the active zone protein, elks, in insulin secretion from pancreatic β-cells
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768504/
https://www.ncbi.nlm.nih.gov/pubmed/31500835
http://dx.doi.org/10.1016/j.molmet.2019.06.017
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