Two structurally distinct and spatially compartmentalized adenylate kinases are expressed from the AK1 gene in mouse brain

Edwin Janssen, Jan Kuiper, Denice Hodgson, Leonid V. Zingman, Alexey E. Alekseev, Andre Terzic, Bé Wieringa

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Adenylate kinases (AK, EC 2.7.4.3) have been considered important enzymes for energy homeostasis and metabolic signaling. To gain a better understanding of their cell-specific significance we studied the structural and functional aspects of products of one adenylate kinase gene, AK1, in mouse tissues. By combined computer database comparison and Northern analysis of mRNAs, we identified transcripts of 0.7 and 2.0 kilobases with different 5′ and 3′ on-coding regions which result from alternative use of promoters and polyadenylation sites. These mRNAs specify two distinct proteins, AK1 and a membrane-bound AK1 isoform (AK1β), which differ in their N-terminal end and are co-expressed in several tissues with high-energy demand, including the brain. Immunohistochemical analysis of brain tissue and primary neurons and astrocytes in culture demonstrated that AK1 isoforms are expressed predominantly in neurons. AK1β, when tested in transfected COS-1 and N2a neuroblastoma cells, located at the cellular membrane and was able to catalyze phosphorylation of ADP in vitro. In addition, AK1β mediated AMP-induced activation of recombinant ATP-sensitive potassium channels in the presence of ATP. Thus, two structurally distinct AK1 isoforms co-exist in the mouse brain within distinct cellular locations. These enzymes may function in promoting energy homeostasis in the compartmentalized cytosol and in translating cellular energetic signals to membrane metabolic sensors.

Original languageEnglish (US)
Pages (from-to)59-72
Number of pages14
JournalMolecular and Cellular Biochemistry
Volume256-257
Issue number1-2
DOIs
StatePublished - Jan 1 2004

Keywords

  • Adenylate kinase
  • Energy homeostasis
  • K channel
  • Metabolic signaling
  • Phosphotransfer

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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