Tropomyosin isoforms from the gamma gene differing at the C-terminus are spatially and developmentally regulated in the brain.

Tropomyosin is an actin-binding protein responsible for stabilizing the actin microfilament system in the cytoskeleton of nonmuscle cells and is involved in processes such as growth, differentiation, and polarity of neuronal cells. From the gamma gene, at least 11 different isoforms have been described, with three different C-terminal exons used (9a, 9c, 9d). The precise roles that the different isoforms play are unknown. To examine the localization and hence determine the function of these isoforms in developing mouse, specific antibodies to exons 9a and 9c were made. These were used with previously developed 9d and N-terminal 1b antibodies on Western blots and immunohistochemical analysis of mouse brains. We were able to show that all three C-termini are used in the brain. 9c isoforms are highly enriched in brain and neural cells, and we also detected significant amounts of 9a-containing isoforms in brain. gamma gene activity is relatively constant in the brain, but the choice of C-terminus is developmentally regulated. A more detailed study of the brain revealed regional expression differences. The hippocampus, cerebellum, and cortex were analyzed in depth and revealed that different isoforms could be sorted into different neuronal compartments, which change with development for 9d. Furthermore, a comparison with a homologous exon to 9c from the alpha-tropomyosin gene showed that expression from these exons is related to the maturational state of the neuron, even though both are sorted differently intracellularly. These data suggest that the large numbers of tropomyosin isoforms are likely to have specific roles in microfilament dynamics and neural cell function.