The TSG101 protein binds to connexins and is involved in connexin degradation

Tanja Auth, Sharazad Schlüter, Stephanie Urschel, Petra Kussmann, Stephan Sonntag, Thorsten Höher, Maria M. Kreuzberg, Radoslaw Dobrowolski, Klaus Willecke

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Gap junctions mediate electrical and metabolic communication between cells in almost all tissues and are proposed to play important roles in cellular growth control, differentiation and embryonic development. Gap junctional communication and channel assembly were suggested to be regulated by interaction of connexins with different proteins including kinases and phosphatases. Here, we identified the tumor susceptibility gene 101 (TSG101) protein to bind to the carboxyterminal tail of connexin45 in a yeast two-hybrid protein interaction screen. Glutathione S-transferase pull down experiments and immunoprecipitation revealed that not only connexin45 but also connexin30.2, -36, and -43 carboxyterminal regions were associated with TSG101 protein in pull down analyses and that connexin31, -43 and -45 co-precipitate with endogenous TSG101 protein in lysates from HM1 embryonic stem cells. TSG101 has been shown to be involved in cell cycle control, transcriptional regulation and turnover of endocytosed proteins. Thus, we decided to study the functional role of this interaction. SiRNA mediated knock down of TSG101 in HM1 embryonic stem cells led to increased levels of connexin43 and -45, prolonged half life of these connexins and increased transfer of microinjected Lucifer yellow. Our results suggest that TSG101 is involved in the degradation of connexins via interaction with connexin proteins.

Original languageEnglish (US)
Pages (from-to)1053-1062
Number of pages10
JournalExperimental Cell Research
Issue number6
StatePublished - Apr 1 2009


  • Connexins
  • Protein interaction
  • RNAi
  • TSG101

ASJC Scopus subject areas

  • Cell Biology


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