C-ERBB2 NEU TRANSFECTION INDUCES GAP JUNCTIONAL COMMUNICATION INCOMPETENCE IN GLIAL-CELLS/

Astrocytes form functional networks that participate in active signali ng in which external stimuli are generated and amplified in many of th e same ways as in neurons. Gap junctions between astrocytes offer the structural avenue by which the electrical and metabolic signals are pr opagated from one cell to another. Little is known about the trafficki ng, assembly, and degradation mechanisms of the major astrocytic gap j unction protein connexin43. We have studied a glial cell line transfec ted with the C-erbB2/neu oncogene (neu(+)), finding severe interruptio n of gap junctional communication after stable transfection. Evidence from Western blotting and phosphorylation studies showed that the proc essing of connexin43 to its higher phosphorylated isoforms is disturbe d. Confocal laser imaging indicates that the major deficit in the neu( +) cells is attributable to a lack in plaque assembly of connexin43. B ecause the neu(+) cells also lack N-CAM proteins and because work from others has indicated a close relationship between communication compe tence and constitutive CAM expression, our data suggest that expressio n of C-erbB2/neu oncogene alters cell-cell association via CAM protein s, which thereby affects gap junction plaque assembly and appropriate phosphorylation of connexin43.