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 amyloid peptide display altered morphology characterized by pronounced membrane ruffling and extensive intercellular appositions. Having observed other cell types in which these features accompany increased connexin43 (Cx43) production and gap junctional communication, we examined Cx43 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 in some cells of cultures processed by immunofluorescence, dye-transfer between some cells microinjected with Lucifer Yellow, and gap junctions between cells examined by EM. Normal and vector-transfected PC12 cells exhibited none of these properties. Increased immunofluorescence in 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 connexins in cells that are not normally coupled or only poorly coupled by gap junctions.
Nagy
J I
JI
Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada.
Hossain
M Z
MZ
Hertzberg
E L
EL
Marotta
C A
CA
D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000096:biosynthesis*; D000818:Animals; D015153:Blotting, Western; D002450:Cell Communication; D018031:Connexin 43 / Q000032:analysis / Q000096:biosynthesis*; D005455:Fluorescent Antibody Technique; D017629:Gap Junctions / Q000502:physiology* / Q000648:ultrastructure; D015870:Gene Expression; D006801:Humans; D008854:Microscopy, Electron; D016716:PC12 Cells; D010446:Peptide Fragments / Q000096:biosynthesis; D051381:Rats; D011994:Recombinant Proteins / Q000032:analysis / Q000096:biosynthesis; D014162:Transfection
D016564:Amyloid beta-Protein Precursor; D018031:Connexin 43; D010446:Peptide Fragments; D011994:Recombinant Proteins