Site-specific connexin phosphorylation is associated with reduced heterocellular communication between smooth muscle and endothelium

Adam C. Straub, Scott R. Johnstone, Katherine R. Heberlein, Michael J. Rizzo, Angela K. Best, Scott A Boitano, Brant E. Isakson

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background/Aims: Myoendothelial junctions (MEJs) represent a specialized signaling domain between vascular smooth muscle cells (VSMC) and endothelial cells (EC). The functional consequences of phosphorylation state of the connexins (Cx) at the MEJ have not been explored. Methods/Results: Application of adenosine 3′,5′-cyclic monophosphate sodium (pCPT) to mouse cremasteric arterioles reduces the detection of connexin 43 (Cx43) phosphorylated at its carboxyl terminal serine 368 site (S368) at the MEJ in vivo. After single-cell microinjection of a VSMC in mouse cremaster arterioles, only in the presence of pCPT was dye transfer to EC observed. We used a vascular cell co-culture (VCCC) and applied the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (PMA) or fibroblast growth factor-2 (FGF-2) to induce phosphorylation of Cx43 S368. This phosphorylation event was associated with a significant reduction in dye transfer and calcium communication. Using a novel method to monitor increases in intracellular calcium across the in vitro MEJ, we noted that PMA and FGF-2 both inhibited movement of inositol 1,4,5-triphosphate (IP3), but to a lesser extent Ca2+. Conclusion: These data indicate that site-specific connexin phosphorylation at the MEJ can potentially regulate the movement of solutes between EC and VSMC in the vessel wall.

Original languageEnglish (US)
Pages (from-to)277-286
Number of pages10
JournalJournal of Vascular Research
Volume47
Issue number4
DOIs
StatePublished - Jun 2010

Fingerprint

Connexins
Endothelium
Smooth Muscle
Communication
Vascular Smooth Muscle
Phosphorylation
Smooth Muscle Myocytes
Connexin 43
Endothelial Cells
Arterioles
Fibroblast Growth Factor 2
Serine
Coloring Agents
Calcium
Inositol 1,4,5-Trisphosphate
Microinjections
Phorbol Esters
Tetradecanoylphorbol Acetate
Coculture Techniques
Adenosine

Keywords

  • Endothelium
  • Gap junction
  • Heterocellular communication
  • Myoendothelial junction
  • Phosphorylation
  • Smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Site-specific connexin phosphorylation is associated with reduced heterocellular communication between smooth muscle and endothelium. / Straub, Adam C.; Johnstone, Scott R.; Heberlein, Katherine R.; Rizzo, Michael J.; Best, Angela K.; Boitano, Scott A; Isakson, Brant E.

In: Journal of Vascular Research, Vol. 47, No. 4, 06.2010, p. 277-286.

Research output: Contribution to journalArticle

Straub, Adam C. ; Johnstone, Scott R. ; Heberlein, Katherine R. ; Rizzo, Michael J. ; Best, Angela K. ; Boitano, Scott A ; Isakson, Brant E. / Site-specific connexin phosphorylation is associated with reduced heterocellular communication between smooth muscle and endothelium. In: Journal of Vascular Research. 2010 ; Vol. 47, No. 4. pp. 277-286.
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