Untitled

Abstract

CapZ is a widely distributed and highly conserved, heterodimeric protein, that nucleates actin polymerization and binds to the barbed ends of actin filaments, preventing the addition or loss of actin monomers. CapZ interaction with actin filaments was shown to be of high affinity and decreased in the presence of PIP2. CapZ was located in nascent Z-lines during skeletal muscle myofibrillogenesis before the striated appearance of thin filaments in sarcomers. In this study, the stabilization and the anchorage of thin filaments were explored through identification of CapZ partners in the Z-line. Fish (sea bass) striated white muscle and its related Z-line proteins were selected since they correspond to the simplest Z-line organization. We report here the interaction between purified CapZ and alpha-actinin, a major component of Z filaments and polar links in Z-discs. Affinity of CapZ for alpha-actinin, estimated by fluorescence and immunochemical assays, is in the microM range. This association was found to be independent of actin and shown to be weakened in the presence of phosphoinositides. Binding contacts on the alpha-actinin molecule lie in the 55 kDa repetitive domain. A model including CapZ/alpha-actinin/titin/actin interactions is proposed considering Luther's 3D Z-line reconstruction.

Remodeling of the sarcomeric cytoskeleton in cardiac ventricular myocytes during heart failure and after cardiac resynchronization therapy

“…These sheets ran laterally and exhibited frequent gaps and extended throughout the myocytes. This pattern is consistent with previous descriptions of α-actinin arrangement in striated muscle [3, 4, 6]. Fig.…”

The vertebrate muscle Z-disc: sarcomere anchor for structure and signalling

“…Nebulin runs along the thin filament and forms the template for thin filament assembly (McElhinny et al 2003). CapZ caps the barbed ends of the actin filaments and interacts strongly with α-actinin and nebulin (Papa et al 1999; Pappas et al 2008). The atomic structures of a few Z-disc components, including actin, α-actinin (from homologous domains), CapZ (Yamashita et al 2003) and the titin-telethonin complex (Zou et al 2006) have been solved recently and there is the exciting possibility of fitting them into high resolution 3D electron tomograms of the Z-disc in the near future.…”

Cyclic mechanical strain of myocytes modifies CapZβ1 post translationally via PKCε

“…However, increased dynamics did not lead to a diffused localization of CapZ. Therefore, it is possible that other partnering proteins, such as α- actinin (Papa et al 1999), anchor CapZ at sites away from the actin binding surface. Changes in actin capping in situations of increased load may support clinical findings of cardiomyopathies and constitutively active PKCα overexpression in transgenic animals and cells (Hankiewicz et al 2008; Strait et al 2001).…”