Titin as a Chromosomal Protein

Abstract

Abstract:We identified titin as a chromosomal protein using a human autoimmune scleroderma serum. We cloned the corresponding gene in the fruitt1y, Drosophila melanogaster. We have demonstrated that titin is not only expressed and localized in striated muscle but is also distributed uniformly on condensed mitotic chromosomes using multiple antibodies directed against different domains of both Drosophila and vertebrate titin. Titin is a giant sarcomeric protein responsible for the elasticity of striated muscle. Titin may also function as a molecular scaffold during myofibril assembly. We hypothesize that titin is a component of chromosomes that may function to determine chromosome structure and provide elasticity, playing a role similar to that proposed for titin in muscle. We have identified mutations in Drosophila Titin (D-Titin) and are characterizing phenotypes in muscle and chromosomes.

Troponin I and Tropomyosin regulate chromosomal stability and cell polarity

“…Titin, a large protein spanning the sarcomere length between Z bands is required for chromosome integrity (Machado and Andrew, 2000) and control of gene expression through one of its kinase domains (Lange et al, 2005). However, the chromosomal effects are not likely to result from a direct binding of titin to chromosomes because a thorough search for proteins associated to metaphase chromosomes of HeLa cells failed to identify it (Takata et al, 2007).…”

Mechanotransduction from the ECM to the genome: Are the pieces now in place?

“…Overexpression of the lamin binding domain of titin disrupted nuclear lamina integrity and produced nuclei that were herniated and misshapen [Zastrow et al, 2006]. Titins are also involved in chromosome condensation and chromosome segregation during mitosis in Drosophila melanogaster embryos [Machado and Andrew, 2000]. Titin bound to the nuclear lamina may give order to chromatin in the nucleus.…”

Micromechanical studies of mitotic chromosomes

“…Although condensin structural maintenance of chromosome (SMC) protein complexes are essential to mitotic condensation (Strunnikov et al 1993, Hirano & Mitchison 1994, Strunnikov et al 1995, Hirano 2006, exactly how these proteins act on chromatin is unknown. Given the many different models for mitotic chromosome structure (Saitoh & Laemmli 1994, Houchmandzadeh & Dimitrov 1999, Kimura et al 1999, Machado & Andrew 2000, Maeshima & Laemmli 2003, Dietzel et al 2004, Kireeva et al 2004, Hirano 2006, Fukui & Uchiyama 2007, it is clear that we do not yet understand large-scale chromosome folding (Belmont 2006).…”