INDUCTION OF CONNEXIN43 AND GAP JUNCTIONAL COMMUNICATION IN PC12 CELLS OVEREXPRESSING THE CARBOXY-TERMINAL REGION OF AMYLOID PRECURSOR PROTEIN

Previous studies have shown that PC12 cells overexpressing beta/A4 amy loid peptide display altered morphology characterized by pronounced me mbrane ruffling and extensive intercellular appositions, Having observ ed other cell types in which these features accompany increased connex in43 (Cx43) production and gap junctional communication, we examined C x43 in normal and beta/A4-transfected PC12 cells, Studies of two beta/ A4-transfected PC12 clones revealed an induction of Cx43 expression by Western blotting, intracellular and plasma membrane-associated Cx43 i n some cells of cultures processed by immunofluorescence, dye-transfer between some cells microinjected with Lucifer Yellow, and gap junctio ns between cells examined by EM, Normal and vector-transfected PC12 ce lls exhibited none of these properties. Increased immunofluorescence i n some clusters of beta/A4-transfected cells was also observed with a monoclonal antibody against connexin32. The results suggest that beta/ A4 amyloid peptide may cause aberrant intercellular communication and gap junction formation through induction or increased expression of co nnexins in cells that are not normally coupled or only poorly coupled by gap junctions. (C) 1996 Wiley-Liss, Inc.