Titin: properties and family relationships

  title={Titin: properties and family relationships},
  author={Larissa Tskhovrebova and John Trinick},
  journal={Nature Reviews Molecular Cell Biology},
In striated muscles, the rapid production of macroscopic levels of force and displacement stems directly from highly ordered and hierarchical protein organization, with the sarcomere as the elemental contractile unit. There is now a wealth of evidence indicating that the giant elastic protein titin has important roles in controlling the structure and extensibility of vertebrate muscle sarcomeres. 
Roles of Titin in the Structure and Elasticity of the Sarcomere
Some recent titin data is reviewed and its implications for sarcomere architecture and elasticity are discussed.
The giant protein titin as an integrator of myocyte signaling pathways.
The titin-associated signalosome includes hotspots of protein-protein interactions important for the regulation of protein quality-control mechanisms, hypertrophic gene activation, and mechanosensing.
Functional and Mutational Analysis of Kinase Domain of the Giant Protein Titin
The giant filamentous muscle protein titin spans half of the sarcomere. Through its tight association with the thick filament, its elastic elements at the I-band, its connection to the cytoskeleton
The sarcomere and sarcomerogenesis.
Striated muscle owes its name to the microscopic appearance, caused by the longitudinal alignment of thousands of highly ordered contractile units, the sarcomeres, and involves the participation of transient scaffolds and adaptors, notably the microtubule network.
The sarcomeric cytoskeleton: from molecules to motion
The sarcomeric cytoskeleton is a system of proteins specific to striated muscle that play a key role in organising the contractile machinery, and integrating and regulating its mechanics and signalling functions.
Assembly and maintenance of the sarcomere night and day.
The sarcomere is being redefined as a dynamic network of proteins capable of generating force and signalling with other cellular compartments and metabolic enzymes capable of controlling many facets of striated myocyte biology.
Titin visualization in real time reveals an unexpected level of mobility within and between sarcomeres
Contrary to prior models in which titin serves as a stable scaffold in sarcomeres, sarcomeric and soluble titin exchange dynamically in myofibers when calcium levels are low.


Cardiac titin: an adjustable multi‐functional spring
It is highlighted that titin is a versatile and adjustable spring with a range of important functions in passive and contracting myocardium, and novel ligands have been identified that link titin to membrane channels, protein turnover and gene expression.
Reverse engineering of the giant muscle protein titin
This work uses protein engineering and single-molecule atomic force microscopy to examine the mechanical components that form the elastic region of human cardiac titin and shows the functional reconstitution of a protein from the sum of its parts.
Elasticity and unfolding of single molecules of the giant muscle protein titin
Mechanical experiments on single molecules of titin are done to determine their visco-elastic properties, showing that there are two main sources of elasticity: one deriving from the entropy of straightening the molecule; the other consistent with extension of the polypeptide chain in the PEVK region.
Titin folding energy and elasticity
In the present experiments, equilibrium unfolding of titin from rabbit skeletal muscles was studied in vitro by fluorescence and circular dichroism spectroscopy, and the data suggest two unfolding transitions, both of which appear cooperative.
Sarcomeric visco-elasticity of chemically skinned skeletal muscle fibres of the rabbit at rest
  • K. Ranatunga
  • Biology
    Journal of Muscle Research & Cell Motility
  • 2004
It is suggested that the velocity-sensitive tension components in intact sarcomere arise from interactions between sarcomeric filaments, filament segments and inter-filamentary medium; the two components of visco-elasticity arise from distinct regions of titin (connectin) molecules.
Titins: Giant Proteins in Charge of Muscle Ultrastructure and Elasticity
The architecture of sequences in the A band region of titin suggests why thick filament structure is conserved among vertebrates and compares two elements that correlate with tissue stiffness that suggest that titin may act as two springs in series.
Hidden complexity in the mechanical properties of titin
It is shown that, under physiological forces, the partly unfolded intermediate does not contribute to mechanical strength, and a unified forced unfolding model of all I27 analogues studied is proposed, which concludes that I27 can withstand higher forces in muscle than was predicted previously.
Association of titin and myosin heavy chain in developing skeletal muscle.
The data suggest that synthesis and assembly of titin and myosin are temporally and spatially coordinated in nascent myofibrils and support the hypothesis that titin molecules help to organize sarcomere formation.
Does titin regulate the length of muscle thick filaments?