| Transgelin-2 (TAGLN2) is a member of the transgelin/calponin family of actin-crosslinking proteins, characterized by a single-domain structure containing a conserved calponin homology (CH) domain (residues ~95-184) that binds along the length of F-actin. Unlike transgelin-1, TAGLN2 lacks VHP motifs but shares 64% sequence homology, with key actin-contacting residues such as Trp137, Asp160, and Arg183 that stabilize actin filaments by competing with cofilin to inhibit filament depolymerization. TAGLN2 is primarily expressed in immune cells, including T and B lymphocytes and macrophages, as well as in smooth muscle and epithelial tissues. It bundles and stabilizes the actin cytoskeleton, thereby regulating cell morphology, motility, and signaling. In T cells, TAGLN2 enhances TCR-induced Ca²⁺ influx through the STIM1-Orai1 pathway, promotes ZAP-70 phosphorylation, and activates downstream signaling pathways such as ERK, NF-κB, and NFAT, facilitating IL-2 production and cell proliferation. It also associates with the LFA-1 integrin to increase adhesion and avidity during immune synapse formation and T cell-mediated cytotoxicity. In B cells, TAGLN2 supports activation and migration via PLCγ2 phosphorylation, facilitates germinal center localization, and promotes B-T cell conjugation. It inhibits Arp2/3-mediated actin branching, favoring the formation of linear, bundled actin structures that support filopodia formation, phagocytosis, and chemotaxis through RhoA signaling pathways. TAGLN2 plays roles in wound healing, embryonic development, and immune surveillance by modulating actin dynamics required for cell migration and invasion. Knockout models reveal impaired T and B effector functions, reduced cytokine responses, and compromised antigen presentation. In disease contexts, TAGLN2 overexpression promotes cancer progression, including in gliomas and hepatocellular carcinoma (HCC) via invadopodia formation and mesenchymal transition, metastasis, and vascular dysfunction (notably through TRPC6), while deficiency diminishes tumor invasion. |
