In animals, it is an important component of the muscular system which works in conjunction with troponin to regulate muscle contraction.

These type of organelles are collectively known as the cytoskeleton, and one of the most ancient systems is based on filamentous polymers of the protein actin.

These proteins consist of rod-shaped coiled-coil hetero- or homo-dimers that lie along the α-helical groove of most actin filaments.

This plays a crucial role in the functionality of higher eukaryotes, with humans expressing more than 5 times as many different proteins (isoforms) as genes through alternative splicing.

The former mechanism is a process by which multiple copies of a gene are generated through unequal crossing over, through tandem duplication, or by translocation.

Alternative splicing is a mechanism wherein exons are either retained in the mRNA or targeted for removal in different combinations to create a diverse array of mRNAs from a single pre-mRNA.

A vast array of tropomyosin isoforms are generated by using a combination of different genes and alternative splicing.

Depending on the promoter and initial exon used, tropomyosin isoforms can be categorized as either high-molecular-weight (HMW, 284 amino acids) or low-molecular-weight (LMW, 248).

The most highly related genes are the α- and γ-genes, utilizing two promoters and differing only with the presence of the unique 2a exon in the α-gene.

[3] Numerous reports detail that tropomyosin isoforms are sorted to different intracellular locations, often associating with actin filament populations that are involved in specific processes.

[15][16][17][18] Direct visualization of spatial segregation of isoforms was initially observed by Burgoyne and Norman and soon after by Lin and co-workers.

[28] It was later found that, when cells were exposed to cytochalasin D, a chemical that results in the disorganization of actin filaments, tropomyosin isoform sorting was disrupted.

Many studies have led to the understanding that tropomyosins perform essential functions and are required in a diverse range of species from yeast, worms, and flies to complex mammals.

The essential role of tropomyosins was discovered in the Bretscher laboratory, where researchers found that, by eliminating the TPM1 gene of budding yeasts, growth rates were reduced, the presence of actin cables disappeared, defects in vesicular transport were observed, and mating of the yeast was poor.

[32] The expression of Tropomyosin 5NM1 in neuronal cells eliminated ADF/cofilin from the growth cone region, leading to more stable actin filaments.

These interactions, under the influence of tropomyosin isoforms, allow actin filaments to be involved in a diverse range of cellular functions.

Myofibrils are composed of repeating protein structures or sarcomeres, the basic functional unit of skeletal muscle.

Binding causes changes in the shape of troponin and subsequently causes the tropomyosin isoform to shift its position on the actin filament.

X-ray diffraction and cryoelectron microscopy suggest that tropomyosin sterically blocks the access of myosin to the actin filament.

Although this model is well-established, it is unclear as to whether the movement of tropomyosin directly causes the myosin head to engage the actin filament.

Smooth muscle may contract spontaneously or rhythmically and be induced by a number of physiochemical agents (hormones, drugs, neurotransmitters).

Smooth muscle is found within the walls of various organs and tubes in the body such as the esophagus, stomach, intestines, bronchi, urethra, bladder, and blood vessels.

A number of regulatory mechanisms, employing many actin-binding proteins, have evolved to control the dynamics of the actin filament system.

It is believed that tropomyosins play a pivotal role in this regulatory system, influencing the associations the actin filament has with other ABPs.

Many studies have shown that there are specific changes to the repertoire of tropomyosins expressed in cells that are undergoing cellular transformation.

A study compared isoform expression between a low- and highly-metastatic Lewis lung carcinoma cell line.

[36][37] The study found that as cells become more metastatic, there is a marked decrease in the expression of HMW tropomyosin 2 protein and mRNA levels.

The elevated number of IgG-producing cells in the colonic mucosa of ulcerative colitis patients is largely committed to producing IgG against Tropomyosin 5-related epitopes.

[47] In both instances, it is unclear as to whether these antibodies play a direct role in the pathogenesis of these human conditions or reflect the high antigenicity of tropomyosins released from compromised cells.

[52] Given the vast array of processes that this protein has been reported to be involved with, there is great interest in tropomyosin isoforms within the scientific community.