Tropomyosin - Isoforms Are Not Functionally Redundant

Isoforms Are Not Functionally Redundant

Many studies have lead 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 they 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. Interestingly when a second yeast gene, TPM2, was deleted no observable changes in the phenotype were recorded, however when deleted in combination with TPM1, it resulted in lethality. This suggests that TPM1 and -2 genes have overlapping function, however TPM2 cannot fully compensate of the loss of TPM1, indicating that some functions of TPM1 are unique. Similar results have been observed in flies, worms, amphibians and mammals, confirming previous results and suggestive of tropomyosin being involved in a wide range of cellular functions. However, the three co-expressed TMP1, 2 and 4 genes cannot compensate for deletion of the TPM3 gene in embryonic stem cells and preimplantation mouse embryos.

Results from gene knockout experiments can be ambiguous and need to be carefully examined. In studies where the deletion of a gene leads to lethality it can at first appear that the gene product had a truly unique role. However lethality can also be the result of the inability of the compromised cell to express other isoforms to rescue the phenotype because the required isoform is not naturally expressed in the cell.