The gap junction channel protein connexin 43 is covalently modified and regulated by SUMOylation

Ane Kjenseth, Tone A. Fykerud, Solveig Sirnes, Jarle Bruun, Zeremariam Yohannes, Matthias Kolberg, Yasufumi Omori, Edgar Rivedal, Edward Leithe

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

SUMOylation is a posttranslational modification in which a member of the small ubiquitin-like modifier (SUMO) family of proteins is conjugated to lysine residues in specific target proteins. Most known SUMOylation target proteins are located in the nucleus, but there is increasing evidence that SUMO may also be a key determinant of many extranuclear processes. Gap junctions consist of arrays of intercellular channels that provide direct transfer of ions and small molecules between adjacent cells. Gap junction channels are formed by integral membrane proteins called connexins, of which the best-studied isoform is connexin 43 (Cx43). Here we show that Cx43 is posttranslationally modified by SUMOylation. The data suggest that theSUMO system regulates the Cx43 protein level and the level of functional Cx43 gap junctions at the plasma membrane. Cx43 was found to be modified by SUMO-1, -2, and -3. Evidence is provided that the membrane-proximal lysines at positions 144 and 237, located in the Cx43 intracellular loop and C-terminal tail, respectively, act asSUMOconjugation sites. Mutations of lysine 144 or lysine 237 resulted in reduced Cx43 SUMOylation and reduced Cx43 protein and gap junction levels. Altogether, these data identify Cx43 as a SUMOylation target protein and represent the first evidence that gap junctions are regulated by the SUMO system.

Original languageEnglish (US)
Pages (from-to)15851-15861
Number of pages11
JournalJournal of Biological Chemistry
Volume287
Issue number19
DOIs
StatePublished - May 4 2012

Fingerprint

Sumoylation
Connexin 43
Connexins
Gap Junctions
Ubiquitin
Lysine
Proteins
Cell membranes
Post Translational Protein Processing
Protein Isoforms
Membrane Proteins
Cell Membrane
Ions
Membranes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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The gap junction channel protein connexin 43 is covalently modified and regulated by SUMOylation. / Kjenseth, Ane; Fykerud, Tone A.; Sirnes, Solveig; Bruun, Jarle; Yohannes, Zeremariam; Kolberg, Matthias; Omori, Yasufumi; Rivedal, Edgar; Leithe, Edward.

In: Journal of Biological Chemistry, Vol. 287, No. 19, 04.05.2012, p. 15851-15861.

Research output: Contribution to journalArticle

Kjenseth, Ane ; Fykerud, Tone A. ; Sirnes, Solveig ; Bruun, Jarle ; Yohannes, Zeremariam ; Kolberg, Matthias ; Omori, Yasufumi ; Rivedal, Edgar ; Leithe, Edward. / The gap junction channel protein connexin 43 is covalently modified and regulated by SUMOylation. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 19. pp. 15851-15861.
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