DEFINING ACTIN FILAMENT LENGTH IN STRIATED MUSCLE: Rulers and Caps or Dynamic Stability?

Abstract

▪ Abstract Actin filaments (thin filaments) are polymerized to strikingly uniform lengths in striated muscle sarcomeres. Yet, actin monomers can exchange dynamically into thin filaments in vivo, indicating that actin monomer association and dissociation at filament ends must be highly regulated to maintain the uniformity of filament lengths. We propose several hypothetical mechanisms that could generate uniform actin filament length distributions and discuss their application to the determination of thin filament length in vivo. At the Z line, titin may determine the minimum extent and tropomyosin the maximum extent of thin filament overlap by regulating α-actinin binding to actin, while a unique Z filament may bind to capZ and regulate barbed end capping. For the free portion of the thin filament, we evaluate possibilities that thin filament components (e.g. nebulin or the tropomyosin/troponin polymer) determine thin filament lengths by binding directly to tropomodulin and regulating pointed end capping,...