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

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

Why New Hybrid Organizations Are Formed: Historical Perspectives on Epistemic and Academic Drift

Abstract in Undetermined By comparing three types of hybrid organizations-18th-century scientific academies, 19th-century institutions of higher vocational education, and 20th-century industrial research institutes-it is the purpose here to answer the question of why new hybrid organizations are continuously formed. Traditionally, and often implicitly, it is often assumed that emerging groups of potential knowledge users have their own organizational preferences and demands influencing the setup of new hybrid organizations. By applying the concepts epistemic and academic drift, it will be argued here, however, that internal organizational dynamics are just as important as changing historical conjunctures in the uses of science when understanding why new hybrid organizations are formed. Only seldom have older hybrid organizations sought to make themselves relevant to new categories of knowledge users as the original ones have been marginalized. Instead, they have tended to accede to ideals supported by traditional academic organizations with higher status in terms of knowledge management, primarily universities. Through this process, demand has been generated for the founding of new hybrid organizations rather than the transformation of existing ones. Although this study focuses on Swedish cases, it is argued that since Sweden strove consistently to implement existing international policy trends during the periods in question, the observations may be generalized to apply to other national and transnational contexts