Effect of Non-Muscle Tropomyosin Isoforms Encoded by the TPM1 Gene on Cofilin-1 Activity toward Actin Filaments

---

Svetlana G. Roman¹, Andrey V. Slushchev¹, Victoria V. Nefedova¹, and Aleksandr M. Matyushenko^1,a*

¹Federal Research Center of Biotechnology, Russian Academy of Sciences, 119071 Moscow, Russia

^* To whom correspondence should be addressed.

Received: July 7, 2025; Revised: September 2, 2025; Accepted: September 16, 2025

---

Actin cytoskeleton is a key participant in numerous cellular processes, including organelle transport, motility, contractility, exocytosis, and endocytosis. It also plays a critical role in pathological processes such as malignant cancer cell invasion. The actin-binding proteins, particularly tropomyosins (Tpm) and cofilins, are involved in actin cytoskeleton remodeling. For this study, we selected the least studied isoforms of Tpm expressed from the TPM1 gene – Tpm1.7, Tpm1.8, and Tpm1.9 – as well as the more well-known Tpm1.1 and Tpm1.6. We investigated mutual influence of these Tpm isoforms and cofilin-1 (cof-1) on actin filament dynamics. Using co-sedimentation assays, we demonstrated that Tpm1.7, Tpm1.8, and Tpm1.9 significantly inhibit cof-1 binding to the F-actin surface. Viscometry was employed to assess depolymerizing and severing effects of cof-1 on actin filaments. Tpm1.1, Tpm1.8, and Tpm1.6 effectively prevented depolymerizing/severing action of cof-1, while the protective effect of Tpm1.7 and Tpm1.9 was less pronounced. The rhodamine-phalloidin displacement assay was used to analyze the cof-1-induced conformational changes in F-actin. All studied Tpm isoforms effectively prevented effects of cof-1 on actin filaments. Our findings indicate that the TPM1 gene products generally exert an inhibitory effect on cof-1 activity in relation to actin filament polymerization/depolymerization dynamics. Such properties of Tpm isoforms could be important for formation of specific intracellular populations of actin filaments.

---

KEY WORDS: actin-binding proteins, tropomyosin, actin, cofilin, actin cytoskeleton dynamics

DOI: 10.1134/S0006297925601467

Publisher’s Note. Pleiades Publishing remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

---