capZ

CapZ is an actin-capping protein that forms a heterodimeric complex capable of binding to the barbed, or plus, ends of actin filaments. In vertebrates the complex is composed of alpha and beta subunits encoded by the CAPZA and CAPZB gene families (for example CAPZA1/2 and CAPZB1/2). CapZ is widely expressed in muscle and non-muscle cells, with a prominent localization at the Z-disc of skeletal and cardiac muscle sarcomeres where it helps organize thin filaments.

Its primary function is to cap the growing barbed ends of actin filaments, preventing polymerization and depolymerization at that end. This capping activity contributes to maintaining filament length and the structural integrity of the sarcomere, and it interacts with other Z-disc components such as alpha-actinin and tropomodulin to coordinate thin-filament organization. In non-muscle cells, CapZ also localizes to actin-rich structures like lamellipodia, where it participates in regulating actin turnover during cell migration.

CapZ activity is regulated by multiple factors. Binding to actin can be modulated by phosphoinositides such as PIP2, as well as by signaling pathways that influence subunit interactions, localization, or affinity for actin. Isoform composition and post-translational modifications can affect capping strength and dynamics, enabling tissue-specific regulation during development or in response to mechanical stress.

Biological significance and research: CapZ is a focus of study in muscle development and disease. Mouse models with altered CapZ function show changes in sarcomere structure and muscle performance, underscoring the role of actin capping in myofibrillar integrity. Across species CapZ is conserved, reflecting its fundamental role in actin cytoskeleton regulation.