A functional channel is necessary for growth suppression by Cx37

Miranda E. Good, Tasha K. Nelson, Alexander M. Simon, Janis M. Burt

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Connexin 37 (Cx37) profoundly suppresses the proliferation of rat insulinoma (Rin) cells by unknown mechanisms. To determine whether a functional pore domain is necessary for Cx37-mediated growth suppression, we introduced a mutation that converted threonine 154 into alanine (T154A). Like other connexins mutated at the homologous site, Cx37-T154A localized to appositional membrane but failed to form functional channels and exerted a dominant-negative effect on coexpressed wild-type Cx37 or Cx43. Unlike the wild-type protein, Cx37-T154A did not suppress the proliferation of Rin cells and did not, with serum deprivation, result in cell cycle arrest. Furthermore, progression through the cell cycle was unaffected by expression of Cx37-T154A. These results indicate that a pore-forming domain that is able to form functional channels is essential for the anti-proliferative, cell-cycle arrest and serum-sensitivity effects of Cx37, and furthermore that the normally localized C-terminal domain is not sufficient for these effects of Cx37.

Original languageEnglish (US)
Pages (from-to)2448-2456
Number of pages9
JournalJournal of Cell Science
Volume124
Issue number14
DOIs
StatePublished - Jul 15 2011

Keywords

  • Cell cycle
  • Connexin 37
  • Gap junction

ASJC Scopus subject areas

  • Cell Biology

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