PLAKOGLOBIN IS ESSENTIAL FOR MYOCARDIAL COMPLIANCE BUT DISPENSABLE FOR MYOFIBRIL INSERTION INTO ADHERENS JUNCTIONS

Plakoglobin (gamma-catenin), a member of the armadillo family of prote ins, is a constituent of the cytoplasmic plaque of cardiac junctions a nd is involved in anchorage of cytoskeletal filaments to specific cadh erins. Its genetic inactivation leads to an embryonic lethal phenotype due to heart dysfunction related to an impairment in the architecture of intercalated discs and in the stability of the heart tissue. To el ucidate the functional consequences of the loss of plakoglobin for myo fibrillar Function, we monitored passive stress-strain relationship an d contractility parameters of demembranated embryonic fibers. Heart fi bers obtained from plakoglobin-deficient embryonic mice were significa ntly less compliant than were fibers from wild-type embryos. This diff erence was especially pronounced at lower fiber extension levels: at 1 20% of slack length, compliance was 2.5-fold lower in plakoglobin-defi cient mice than in the corresponding wild-type group. Contractile para menters (force per cross-section; Ca2+ sensitivity of isometric force and shortening velocity at near-zero load) were comparable in all expe rimental groups. Therefore, we suggest that plakoglobin is important f or cardiac compliance but not necessary for the attachment of the myof ibrillar apparatus to adherens junctions. Thus, we conclude that the l oss of function of desmosomes and the profound disarrangement of junct ional components in plakoglobin null embryos is associated with a decr eased passive compliance, which may explain the ventricular rupture an d consequent pericardial tamponade in embryos lacking plakoglobin. J. Cell. Biochem. 72:8-15, 1999. (C) 1998 Wiley-Liss. Inc.