C-erbB2/neu transfection induces gap junctional communication incompetence in glial cells.
Astrocytes form functional networks that participate in active signaling in which external stimuli are generated and amplified in many of the same ways as in neurons. Gap junctions between astrocytes offer the structural avenue by which the electrical and metabolic signals are propagated from one cell to another. Little is known about the trafficking, assembly, and degradation mechanisms of the major astrocytic gap junction protein connexin43. We have studied a glial cell line transfected with the C-erbB2/neu oncogene (neu+), finding severe interruption of gap junctional communication after stable transfection. Evidence from Western blotting and phosphorylation studies showed that the processing of connexin43 to its higher phosphorylated isoforms is disturbed. Confocal laser imaging indicates that the major deficit in the neu+ cells is attributable to a lack in plaque assembly of connexin43. Because the neu+ cells also lack N-CAM proteins and because work from others has indicated a close relationship between communication competence and constitutive CAM expression, our data suggest that expression of C-erbB2/neu oncogene alters cell-cell association via CAM proteins, which thereby affects gap junction plaque assembly and appropriate phosphorylation of connexin43.
Hofer
A
A
Institute of Anatomy, University of Regensburg, Germany.
Sáez
J C
JC
Chang
C C
CC
Trosko
J E
JE
Spray
D C
DC
Dermietzel
R
R
D000818:Animals; D002478:Cells, Cultured; D018031:Connexin 43 / Q000502:physiology; D017629:Gap Junctions / Q000502:physiology*; D018734:Genes, erbB-2; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009457:Neuroglia / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
D018031:Connexin 43