EFFECT OF NON-MUSCLE TROPOMYOSIN ISOFORMS ENCODED BY THE TPM1 GENE ON COFILIN-1 ACTIVITY TOWARD ACTIN FILAMENTS

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The actin cytoskeleton is an integral participant in a large number of cellular processes, such as organelle transport, motility, contractility, exocytosis and endocytosis. At the same time, it plays an important role in pathological processes, for example, malignant invasion of cancer cells. Actin-binding proteins, in particular proteins of the tropomyosin family (Tpm) and cofilins, participate in the remodeling of the actin cytoskeleton. For the study, we selected the least studied Tpm isoforms expressed from the TPM1 gene – Tpm1.7, Tpm1.8, and Tpm1.9 – as well as the more well-known Tpm1.1 and Tpm1.6. In this work, we studied the mutual influence of these Tpm isoforms and cofilin-1 (cof-1) on the dynamics of the actin cytoskeleton. Using the method of co-precipitation of these proteins, it was shown that Tpm1.7, Tpm1.8 and Tpm1.9 isoforms significantly interfere with cof-1 binding to the F-actin surface. Viscometry was used to evaluate the depolymerizing and severing effect of cof-1 on actin filament. Isoforms Tpm1.1, Tpm1.8, and Tpm1.6 effectively prevented the depolymerizing/severing effect of cof-1, while the protective effect of Tpm1.7 and Tpm1.9 was less pronounced. The rhodamine-phalloidin release assay was used to analyze conformational changes in F-actin induced by cof-1. All studied Tpm isoforms effectively prevented the effect of cof-1 on actin filament. The study showed that TPM1 gene products generally have an inhibitory effect on cof-1 activity in relation to the dynamics of actin filament polymerization/depolymerization. Such properties of Tpm isoforms may be important for the formation of specific intracellular populations of actin filaments.

Sobre autores

S. Roman

Research Center of Biotechnology of the Russian Academy of Sciences

Moscow, Russia

A. Slushchev

Research Center of Biotechnology of the Russian Academy of Sciences

Moscow, Russia

V. Nefedova

Research Center of Biotechnology of the Russian Academy of Sciences

Moscow, Russia

A. Matyushenko

Research Center of Biotechnology of the Russian Academy of Sciences

Email: ammatyushenko@mail.ru
Moscow, Russia

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