A Titan but not Necessarily a Ruler: Assessing the Role of Titin During Thick Filament Patterning and Assembly

@article{Myhre2014ATB,
  title={A Titan but not Necessarily a Ruler: Assessing the Role of Titin During Thick Filament Patterning and Assembly},
  author={John L. Myhre and David B. Pilgrim},
  journal={The Anatomical Record},
  year={2014},
  volume={297}
}
The sarcomeres of striated muscle are among the most elaborate and dynamic eukaryotic cellular protein machinery, and the mechanisms by which these semicrystalline filament networks are initially patterned and assembled remain contentious. In addition to the acto‐myosin filaments that provide motor function, the sarcomere contains titin filaments, comprised of individual molecules of the giant Ig‐ and fibronectin domain‐rich protein titin. Titin is the largest known protein, containing many… 
Titin N2A Domain and Its Interactions at the Sarcomere
TLDR
This review highlights structural conformations of N2A, its predisposition for protein–protein interactions, and its multiple interacting protein partners that allow the modulation of titin’s biological effects.
Thick Filament Protein Network, Functions, and Disease Association.
TLDR
Current knowledge on the molecular structure, subcellular localization, interacting partners, function, modulation via posttranslational modifications, and disease involvement of these five major proteins that comprise the thick filament of striated muscle cells are summarized.
Chaperones and the Proteasome System: Regulating the Construction and Demolition of Striated Muscle
TLDR
The roles of chaperones in sarcomere assembly, the importance ofChaperone homeostasis and the cooperation of chacherones and the UPS in Sarcomere integrity and disease are reviewed.
Mitochondrial abnormalities in the myofibrillar myopathies
TLDR
The literature was reviewed to determine the extent of mitochondrial dysfunction in each of the myofibrillar myopathy subtypes, and a high frequency of COX‐negative or ragged red fibres, a characteristic finding in some of the conventional mitochondrial myopathies, is a rare finding.
Recent Advances in Muscle Research
TLDR
Conclusions in this special issue of The Anatomical Record are focused on myofibrillar proteins, their interactions, and their involvement in myopathies, as well as on aspects of muscle structure and function and progress in understanding the requirements for the assembly and maintenance of muscle.
The genetic basis of resistance to the Ryanodine Receptor modulator chlorantraniliprole in Drosophila melanogaster
TLDR
This research reveals that a novel muscleassociated gene, Stretchin Myosin Light Kinase, is strongly associated with resistance in the DGRP and demonstrates that alleles of large effect are preexisting in naïve populations and such alleles may increase in frequency as this class of insecticides become more widespread.
Using Zebrafish to Analyze the Genetic and Environmental Etiologies of Congenital Heart Defects.
TLDR
The unique toolset available to zebrafish researchers and how those tools are used to interrogate the genetic and environmental contributions to CHDs are examined.
The Physiology of Muscle
  • B. Klein
  • Biology
    Cunningham's Textbook of Veterinary Physiology
  • 2020
...
...

References

SHOWING 1-10 OF 105 REFERENCES
Palindromic assembly of the giant muscle protein titin in the sarcomeric Z-disk
TLDR
This work shows, using X-ray crystallography, how the amino terminus of the longest filament component, the giant muscle protein titin, is assembled into an antiparallel (2:1) sandwich complex by the Z-disk ligand telethonin.
A functional knock-out of titin results in defective myofibril assembly.
TLDR
These experiments provide the first direct evidence for the crucial role of titin in both thick filament formation as a molecular ruler and in the coordination of myofibrillogenesis.
The giant protein titin: a major player in myocardial mechanics, signaling, and disease.
TLDR
This study focuses on recent findings vis-à-vis titin's molecular spring segments in cardiac titins, including the discovery of fetal cardiac isoforms with novel spring elements and new insights regarding the role of titin as a biomechanical sensor and signaling molecule.
M line–deficient titin causes cardiac lethality through impaired maturation of the sarcomere
TLDR
This study uses a titin M line–deficient mouse to show that the initial assembly of the sarcomere does not depend on titin's M-line region or the phosphorylation of T-cap by the titin kinase, and suggests diverse functions for titIn's M line in embryonic development and the adult heart that not only involve the differential expression of titin isoforms but also of titIn-binding proteins.
Muscle giants: molecular scaffolds in sarcomerogenesis.
TLDR
The structure and function of titin, nebulin, and obscurin are reviewed, with the literature supporting a role for them as scaffolding molecules and the contradictory evidence regarding their roles as molecular guides in sarcomerogenesis.
Integration of titin into the sarcomeres of cultured differentiating human skeletal muscle cells.
TLDR
It is proposed that during this transition the large titin molecule is unfolded, with the amino terminus of the molecule migrating in the direction of the Z-line and the carboxy terminus moving towards the M-line in maturated, fused myotubes.
At the Start of the Sarcomere: A Previously Unrecognized Role for Myosin Chaperones and Associated Proteins during Early Myofibrillogenesis
TLDR
Several lines of evidence are outlined that converge to build a model for Unc45b activity during early myofibrillogenesis, which may involve functional control of nonmuscle myosins during the earliest stages of myogenesis, when premyofibril scaffolds are first formed from dynamic cytoskeletal actin.
Assembly of titin, myomesin and M-protein into the sarcomeric M band in differentiating human skeletal muscle cells in vitro.
TLDR
The distribution patterns of different epitopes recognized by newly developed antibodies against the extreme carboxyterminal portion of titin that is anchored in the M band, during the in vitro differentiation of human skeletal muscle cells are described.
...
...