Selective effect of PDGF on connexin43 versus connexin40 comprised gap junction channels

Janis M. Burt, Timothy D. Steele

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The goals of the current study were to determine whether the conductance of Cx40 and Cx40-Cx43 mixed composition junctions was regulated by platelet-derived growth factor (PDGF)-activated signaling cascades, to ascertain the minimum number of Cx43 subunits/connexon required to confer PDGF sensitivity, and to identify specific residues in Cx43 required for this regulation. Junctional and channel conductances (gj and γj, respectively) were determined for Cx40/Cx40, Cx43/Cx43, Cx40/Cx43, and Cx40-Cx43/Cx40-Cx43 mixed composition channels. PDGF had no effect on gj in Cx40/Cx40 pairs, but decreased gj in the remaining combinations by 53% (Cx43/Cx43), 48% (Cx40/Cx43), 41% (4:1 Cx40:Cx43 expression ratio) and 24% (10:1 Cx40:Cx43 expression ratio). Based on the predicted connexin composition of channels in cells expressing Cx40 and Cx43 at either 4:1 or 10:1 ratios, these decreases in gj suggest that a single subunit of Cx43 is sufficient to confer PDGF sensitivity. The effect of PDGF on gj involved a decrease in both γj and Po and required serine 368 in the C-terminus. These data implicate protein kinase C as the mediator of the PDGF effect and strongly suggest that acute regulation of gap junction function by PDGF-activated signaling cascades is conferred by low levels of expression of a sensitive connexin in cells that otherwise express insensitive connexins.

Original languageEnglish (US)
Pages (from-to)287-291
Number of pages5
JournalCell Communication and Adhesion
Volume10
Issue number4-6
StatePublished - Jul 1 2003

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Keywords

  • Connexin40
  • Connexin43
  • Gap junction
  • PDGF
  • Permselectivity

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology

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