Phosphorylation at S365 is a gatekeeper event that changes the structure of Cx43 and prevents downregulation by PKC

Joell L. Solan, Lucrecia Marquez-Rosado, Paul L Sorgen, Perry J. Thornton, Philip R. Gafken, Paul D. Lampe

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Phosphorylation at unspecified sites is known to regulate the life cycle (assembly, gating, and turnover) of the gap junction protein, Cx43. In this paper, we show that Cx43 is phosphorylated on S365 in cultured cells and heart tissue. Nuclear magnetic resonance structural studies of the C-terminal region of Cx43 with an S365D mutation indicate that it forms a different stable conformation than unphosphorylated wild-type Cx43. Immunolabeling with an antibody specific for Cx43 phosphorylated at S365 shows staining on gap junction structures in heart tissue that is lost upon hypoxia when Cx43 is no longer specifically localized to the intercalated disk. Efficient phosphorylation at S368, an important Cx43 channel regulatory event that increases during ischemia or PKC activation, depends on S365 being unphosphorylated. Thus, phosphorylation at S365 can serve a "gatekeeper" function that may represent a mechanism to protect cells from ischemia and phorbol ester-induced down-regulation of channel conductance.

Original languageEnglish (US)
Pages (from-to)1301-1309
Number of pages9
JournalJournal of Cell Biology
Volume179
Issue number6
DOIs
StatePublished - Dec 17 2007

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Connexin 43
Down-Regulation
Phosphorylation
Ischemia
Connexins
Gap Junctions
Phorbol Esters
Life Cycle Stages
Cultured Cells
Magnetic Resonance Spectroscopy
Staining and Labeling
Mutation
Antibodies

ASJC Scopus subject areas

  • Cell Biology

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Phosphorylation at S365 is a gatekeeper event that changes the structure of Cx43 and prevents downregulation by PKC. / Solan, Joell L.; Marquez-Rosado, Lucrecia; Sorgen, Paul L; Thornton, Perry J.; Gafken, Philip R.; Lampe, Paul D.

In: Journal of Cell Biology, Vol. 179, No. 6, 17.12.2007, p. 1301-1309.

Research output: Contribution to journalArticle

Solan, Joell L. ; Marquez-Rosado, Lucrecia ; Sorgen, Paul L ; Thornton, Perry J. ; Gafken, Philip R. ; Lampe, Paul D. / Phosphorylation at S365 is a gatekeeper event that changes the structure of Cx43 and prevents downregulation by PKC. In: Journal of Cell Biology. 2007 ; Vol. 179, No. 6. pp. 1301-1309.
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AU - Marquez-Rosado, Lucrecia

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AU - Gafken, Philip R.

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