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Andreas Lindqvist

Andreas Lindqvist

Research engineer

Andreas Lindqvist

Nuclear import of glucokinase in pancreatic beta-cells is mediated by a nuclear localization signal and modulated by SUMOylation

Author

  • Bente Berg Johansson
  • Karianne Fjeld
  • Marie Holm Solheim
  • Jun Shirakawa
  • Enming Zhang
  • Magdalena Keindl
  • Jiang Hu
  • Andreas Lindqvist
  • Anne Døskeland
  • Gunnar Mellgren
  • Torgeir Flatmark
  • Pål Rasmus Njølstad
  • Rohit N. Kulkarni
  • Nils Wierup
  • Ingvild Aukrust
  • Lise Bjørkhaug

Summary, in English

The localization of glucokinase in pancreatic beta-cell nuclei is a controversial issue. Although previous reports suggest such a localization, the mechanism for its import has so far not been identified. Using immunofluorescence, subcellular fractionation and mass spectrometry, we present evidence in support of glucokinase localization in beta-cell nuclei of human and mouse pancreatic sections, as well as in human and mouse isolated islets, and murine MIN6 cells. We have identified a conserved, seven-residue nuclear localization signal (30LKKVMRR36) in the human enzyme. Substituting the residues KK31,32 and RR35,36 with AA led to a loss of its nuclear localization in transfected cells. Furthermore, our data indicates that SUMOylation of glucokinase modulates its nuclear import, while high glucose concentrations do not significantly alter the enzyme nuclear/cytosolic ratio. Thus, for the first time, we provide data in support of a nuclear import of glucokinase mediated by a redundant mechanism, involving a nuclear localization signal, and which is modulated by its SUMOylation. These findings add new knowledge to the functional role of glucokinase in the pancreatic beta-cell.

Department/s

  • Diabetes - Islet Patophysiology
  • Neuroendocrine Cell Biology
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2017-06-22

Language

English

Pages

146-157

Publication/Series

Molecular and Cellular Endocrinology

Volume

454

Document type

Journal article

Publisher

Elsevier

Topic

  • Endocrinology and Diabetes

Keywords

  • Beta-cells
  • Glucokinase
  • Human islets
  • MIN6 cells
  • Nuclear localization signal
  • Pancreatic islets
  • SUMOylation

Status

Published

Research group

  • Diabetes - Islet Patophysiology
  • Neuroendocrine Cell Biology

ISBN/ISSN/Other

  • ISSN: 0303-7207