Capping Protein (Actin Filament) Muscle Z-Line Alpha 2, also known as CAPZA2, is a crucial protein involved in the regulation of actin filament dynamics. This protein is a part of the F-actin capping protein alpha subunit family and plays a significant role in muscle function by capping the barbed ends of actin filaments, thereby regulating their growth and stability .
The CAPZA2 gene is located on human chromosome 7, specifically at position q31.2-q31.3 . The gene encodes a protein that is approximately 33.0 kDa in size and composed of 286 amino acids . The primary sequence of CapZ-alpha2 contains three C-terminal, regularly spaced leucines at positions 258, 262, and 266, which are critical for actin binding . These residues are conserved within the CapZ-beta isoform, highlighting the importance of these sequences in the protein’s function .
CapZ-alpha2 binds to the barbed ends of actin filaments in a calcium-independent manner, preventing the addition or loss of actin monomers at these ends . This capping action is essential for the regulation of actin filament dynamics, which is crucial for various cellular processes, including cell motility, division, and muscle contraction . Unlike other capping proteins such as gelsolin and severin, CapZ-alpha2 does not sever actin filaments .
CapZ-alpha2 is predominantly expressed in cardiac and skeletal muscle tissues, where it caps sarcomeric actin at Z-discs . This capping action is vital for the organization and stability of myofilaments during myofibrillogenesis, the process by which muscle fibers are formed . CapZ-alpha2 is present at Z-discs in muscle cells before the striation of actin filaments, suggesting that it plays a role in directing the polarity and organization of sarcomeric actin during I-band formation .
Mutations or dysregulation of the CAPZA2 gene have been associated with various diseases, including nonobstructive coronary artery disease and autosomal recessive deafness . Understanding the function and regulation of CapZ-alpha2 is crucial for developing therapeutic strategies for these conditions.