Expression of CD38 with intracellular enzymatic activity: A possible explanation for the insulin release induced by intracellular cADPR

Yasuhiko Ohta, Akira Kitanaka, Keichiro Mihara, Osamu Imataki, Hiroaki Ohnishi, Terukazu Tanaka, Tomohiko Taminato, Yoshitsugu Kubota

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

CD38 is a transmembrane glycoprotein expressed in multiple cell types, including pancreatic β cells. It can serve as an enzyme that catalyzes the metabolism of two different Ca2+-mobilizing compounds, cyclic adenosine diphosphoribose (cADPR) and nicotinic acid adenine dinucleotide phosphate. One of these metabolites, cADPR, is known to be involved in glucose-induced insulin secretion from pancreatic β cells. Although the essential role of CD38 for endogenous cADPR synthesis has been established, the relationship between the proposed extracellular enzymatic activity of CD38 and the intracellular Ca2+ modulation caused by the intracellular cADPR accumulation has not yet been fully explained. For a better understanding of the role of CD38 in the insulin secretion machinery, analysis of the intracellular localization of this molecule in pancreatic β cells is essential. In an attempt to provide a method to probe the N-terminal and C-terminal of CD38 separately, we generated an insulin-secreting MIN6 murine pancreatic β cell line expressing a human CD38 bearing an N-terminal FLAG epitope tag. We found a weak but consistent expression of the FLAG epitope outside of the cells, indicating the presence of a small amount of CD38 with cytoplasmic enzymatic activity. MIN6 cells transfected with human CD38 exhibited increased glucose-induced insulin release. In addition, anti-FLAG cross-linking further enhanced the insulin release, suggesting that the N-terminal of CD38 expressed on the cell surface functions as a receptor for an unknown ligand and triggers positive signals for insulin secretion.

Original languageEnglish
Pages (from-to)293-299
Number of pages7
JournalMolecular and Cellular Biochemistry
Volume352
Issue number1-2
DOIs
Publication statusPublished - 06-2011

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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