Hypothetical mechanisms involving titin, tropomyosin, nebulin, and tropomodulin are proposed to explain how uniform actin filament lengths are maintained in striated muscle sarcomeres.
This review outlines theoretical molecular mechanisms by which striated muscle maintains uniform actin filament lengths despite dynamic monomer exchange.
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 alpha-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, or alternatively, that myosin thick filaments, together with titin, determine filament length by indirectly regulating tropomodulin's capping activity.
Littlefield et al. (1998) conducted a review in Striated muscle physiology. Hypothetical mechanisms involving titin, tropomyosin, nebulin, and tropomodulin are proposed to explain how uniform actin filament lengths are maintained in striated muscle sarcomeres.