Abstract
Many proteins contribute to the contractile properties of muscles, most notably myosin thick filaments, which are anchored at the M-line, and actin thin filaments, which are anchored at the Z-discs that border each sarcomere. In humans, mutations in the actin-binding protein Filamin-C result in myopathies, but the underlying molecular function is not well understood. Here we show using Drosophila indirect flight muscle that the filamin ortholog Cheerio in conjunction with the giant elastic protein titin plays a crucial role in keeping thin filaments stably anchored at the Z-disc. We identify the filamin domains required for interaction with the titin ortholog Sallimus, and we demonstrate a genetic interaction of filamin with titin and actin. Filamin mutants disrupting the actin- or the titin-binding domain display distinct phenotypes, with Z-discs breaking up in parallel or perpendicularly to the myofibril, respectively. Thus, Z-discs require filamin to withstand the strong contractile forces acting on them.
Highlights
The most complex actin-related cellular structure is the sarcomere, the basic contractile unit of muscle cells
We show that filamin mainly serves as a Z-disc cohesive element, binding both thin filaments and titin
This configuration enables filamin to act as a bridge between thin filaments and the elastic scaffold protein titin from the adjacent sarcomere, maintaining sarcomere stability during muscle contraction
Summary
The most complex actin-related cellular structure is the sarcomere, the basic contractile unit of muscle cells. The sarcomere consists of antiparallel actin thin filaments and myosin thick filaments. Filamin function in muscles both ends of the sarcomere. In the center of the sarcomere is the M-line, another giant protein complex, that docks the thick filaments. The Z-disc is part of the I-band region, characterized by the absence of myosin. The M-line is at the center of the H-zone region, devoid of actin [1]. The sliding of thick filaments along the thin filaments pulls the Z-disc towards the M-line, representing the basis of muscle contraction [1]
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