Neuronal calcium sensor-1 potentiates glucose-dependent exocytosis in pancreatic β cells through activation of phosphatidylinositol 4-kinase β

Jesper Gromada, Christina Bark, Kamille Smidt, Alexander M. Efanov, Juliette Janson, Slavena A. Mandic, Dominic Luc Webb, Wei Zhang, Björn Meister, Andreas Jeromin, Per Olof Berggren

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Cytosolic free Ca2+ plays an important role in the molecular mechanisms leading to regulated insulin secretion by the pancreatic β cell. A number of Ca2+-binding proteins have been implicated in this process. Here, we define the role of the Ca2+-binding protein neuronal Ca2+ sensor-1 (NCS-1) in insulin secretion. In pancreatic β cells, NCS-1 increases exocytosis by promoting the priming of secretory granules for release and increasing the number of granules residing in the readily releasable pool. The effect of NCS-1 on exocytosis is mediated through an increase in phosphatidylinositol (PI) 4-kinase β activity and the generation of phosphoinositides, specifically PI 4-phosphate and PI 4,5-bisphosphate. In turn, PI 4,5-bisphosphate controls exocytosis through the Ca2+-dependent activator protein for secretion present in β cells. Our results provide evidence for an essential role of phosphoinositide synthesis in the regulation of glucose-induced insulin secretion by the pancreatic β cell. We also demonstrate that NCS-1 and its downstream target, PI 4-kinase β;, are critical players in this process by virtue of their capacity to regulate the release competence of the secretory granules.

Original languageEnglish
Pages (from-to)10303-10308
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number29
DOIs
StatePublished - Jul 19 2005
Externally publishedYes

Fingerprint

1-Phosphatidylinositol 4-Kinase
Exocytosis
Phosphatidylinositols
Glucose
Secretory Vesicles
Insulin
Carrier Proteins
Mental Competency
frequenin calcium sensor proteins
Proteins

Keywords

  • Ca-dependent activator protein for secretion
  • Insulin
  • Islet
  • Phosphoinositides
  • Secretion

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Neuronal calcium sensor-1 potentiates glucose-dependent exocytosis in pancreatic β cells through activation of phosphatidylinositol 4-kinase β. / Gromada, Jesper; Bark, Christina; Smidt, Kamille; Efanov, Alexander M.; Janson, Juliette; Mandic, Slavena A.; Webb, Dominic Luc; Zhang, Wei; Meister, Björn; Jeromin, Andreas; Berggren, Per Olof.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 29, 19.07.2005, p. 10303-10308.

Research output: Contribution to journalArticle

Gromada, Jesper ; Bark, Christina ; Smidt, Kamille ; Efanov, Alexander M. ; Janson, Juliette ; Mandic, Slavena A. ; Webb, Dominic Luc ; Zhang, Wei ; Meister, Björn ; Jeromin, Andreas ; Berggren, Per Olof. / Neuronal calcium sensor-1 potentiates glucose-dependent exocytosis in pancreatic β cells through activation of phosphatidylinositol 4-kinase β. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 29. pp. 10303-10308.
@article{25d544face2e4713b8887232d7568cf3,
title = "Neuronal calcium sensor-1 potentiates glucose-dependent exocytosis in pancreatic β cells through activation of phosphatidylinositol 4-kinase β",
abstract = "Cytosolic free Ca2+ plays an important role in the molecular mechanisms leading to regulated insulin secretion by the pancreatic β cell. A number of Ca2+-binding proteins have been implicated in this process. Here, we define the role of the Ca2+-binding protein neuronal Ca2+ sensor-1 (NCS-1) in insulin secretion. In pancreatic β cells, NCS-1 increases exocytosis by promoting the priming of secretory granules for release and increasing the number of granules residing in the readily releasable pool. The effect of NCS-1 on exocytosis is mediated through an increase in phosphatidylinositol (PI) 4-kinase β activity and the generation of phosphoinositides, specifically PI 4-phosphate and PI 4,5-bisphosphate. In turn, PI 4,5-bisphosphate controls exocytosis through the Ca2+-dependent activator protein for secretion present in β cells. Our results provide evidence for an essential role of phosphoinositide synthesis in the regulation of glucose-induced insulin secretion by the pancreatic β cell. We also demonstrate that NCS-1 and its downstream target, PI 4-kinase β;, are critical players in this process by virtue of their capacity to regulate the release competence of the secretory granules.",
keywords = "Ca-dependent activator protein for secretion, Insulin, Islet, Phosphoinositides, Secretion",
author = "Jesper Gromada and Christina Bark and Kamille Smidt and Efanov, {Alexander M.} and Juliette Janson and Mandic, {Slavena A.} and Webb, {Dominic Luc} and Wei Zhang and Bj{\"o}rn Meister and Andreas Jeromin and Berggren, {Per Olof}",
year = "2005",
month = "7",
day = "19",
doi = "10.1073/pnas.0504487102",
language = "English",
volume = "102",
pages = "10303--10308",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "29",

}

TY - JOUR

T1 - Neuronal calcium sensor-1 potentiates glucose-dependent exocytosis in pancreatic β cells through activation of phosphatidylinositol 4-kinase β

AU - Gromada, Jesper

AU - Bark, Christina

AU - Smidt, Kamille

AU - Efanov, Alexander M.

AU - Janson, Juliette

AU - Mandic, Slavena A.

AU - Webb, Dominic Luc

AU - Zhang, Wei

AU - Meister, Björn

AU - Jeromin, Andreas

AU - Berggren, Per Olof

PY - 2005/7/19

Y1 - 2005/7/19

N2 - Cytosolic free Ca2+ plays an important role in the molecular mechanisms leading to regulated insulin secretion by the pancreatic β cell. A number of Ca2+-binding proteins have been implicated in this process. Here, we define the role of the Ca2+-binding protein neuronal Ca2+ sensor-1 (NCS-1) in insulin secretion. In pancreatic β cells, NCS-1 increases exocytosis by promoting the priming of secretory granules for release and increasing the number of granules residing in the readily releasable pool. The effect of NCS-1 on exocytosis is mediated through an increase in phosphatidylinositol (PI) 4-kinase β activity and the generation of phosphoinositides, specifically PI 4-phosphate and PI 4,5-bisphosphate. In turn, PI 4,5-bisphosphate controls exocytosis through the Ca2+-dependent activator protein for secretion present in β cells. Our results provide evidence for an essential role of phosphoinositide synthesis in the regulation of glucose-induced insulin secretion by the pancreatic β cell. We also demonstrate that NCS-1 and its downstream target, PI 4-kinase β;, are critical players in this process by virtue of their capacity to regulate the release competence of the secretory granules.

AB - Cytosolic free Ca2+ plays an important role in the molecular mechanisms leading to regulated insulin secretion by the pancreatic β cell. A number of Ca2+-binding proteins have been implicated in this process. Here, we define the role of the Ca2+-binding protein neuronal Ca2+ sensor-1 (NCS-1) in insulin secretion. In pancreatic β cells, NCS-1 increases exocytosis by promoting the priming of secretory granules for release and increasing the number of granules residing in the readily releasable pool. The effect of NCS-1 on exocytosis is mediated through an increase in phosphatidylinositol (PI) 4-kinase β activity and the generation of phosphoinositides, specifically PI 4-phosphate and PI 4,5-bisphosphate. In turn, PI 4,5-bisphosphate controls exocytosis through the Ca2+-dependent activator protein for secretion present in β cells. Our results provide evidence for an essential role of phosphoinositide synthesis in the regulation of glucose-induced insulin secretion by the pancreatic β cell. We also demonstrate that NCS-1 and its downstream target, PI 4-kinase β;, are critical players in this process by virtue of their capacity to regulate the release competence of the secretory granules.

KW - Ca-dependent activator protein for secretion

KW - Insulin

KW - Islet

KW - Phosphoinositides

KW - Secretion

UR - http://www.scopus.com/inward/record.url?scp=22544483517&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=22544483517&partnerID=8YFLogxK

U2 - 10.1073/pnas.0504487102

DO - 10.1073/pnas.0504487102

M3 - Article

VL - 102

SP - 10303

EP - 10308

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 29

ER -