Abba is an essential TRIM/RBCC protein for maintaining the integrity of sarcomeric cytoarchitecture

Abstract

Organized sarcomeric striations represent an evolutionarily conserved hallmark of functional skeletal muscles. Here, we demonstrate that the Drosophila Abba protein, a member of the TRIM/RBCC superfamily, has a pivotal regulatory role in maintaining proper sarcomeric cytoarchitecture during development and muscle usage. abba mutant embryos initially form muscles, but F-actin and Myosin striations become progressively disrupted when the muscles undergo growth and endure increased contractile forces during larval development. Abnormal Myosin aggregates and myofiber atrophy are also notable in the abba mutants. The larval defects result in compromised muscle function, and hence important morphogenetic events do not occur properly during pupation, leading to lethality. Abba is localized at larval Z-discs, and genetic evidence indicates that abba interacts with α-actinin, kettin/D-titin, and mlp84B, genes that encode important Z-disc proteins for stable myofibrillar organization and optimal muscle function. RNAi experiments and ultrastructural analysis reveal that Abba has an additional crucial role in sarcomere maintenance in adult muscles. Abba is required for ensuring the integrity and function of Z-discs and M-lines. Rescue experiments further show that Abba function is dependent upon its B-box/coiled-coil domain, NHL repeats, and RING finger domain. The importance of these presumed protein-protein interaction and ubiquitin ligase-associated domains supports our hypothesis that Abba is needed for specific protein complex formation and stabilization at Z-discs and M-lines.