Abstract
TAGLN is an actin-binding protein family that comprises three isoforms with theorized roles in smooth muscle differentiation, tumour development, lymphocyte activation, and brain chemistry. However, their fundamental characteristics in regulation of the actin-based cytoskeleton are not fully understood. Here we show that TAGLN2 (including TAGLN1 and TAGLN3) extensively nucleates G-actin polymerization under low-salt conditions, where polymerization would be completely suppressed. The calponin homology domain and actin-binding loop are essential to mechanically connect two adjacent G-actins, thereby mediating multimeric interactions. However, TAGLN2 blocked the Arp2/3 complex binding to actin filaments under physiological salt conditions, thereby inhibiting branched actin nucleation. In HeLa and T cells, TAGLN2 enhanced filopodium-like membrane protrusion. Collectively, the dual functional nature of TAGLN2—G-actin polymerization and Arp2/3 complex inhibition—may account for the mechanisms of filopodia development at the edge of Arp2/3-rich lamellipodia in various cell types.
Highlights
The TAGLN superfamily comprises TAGLN1, 2, and 3 isoforms, which have high degrees of sequence identity (~80%)
Using high-speed co-sedimentation assay, we unexpectedly observed that TAGLN2 binds to G-actin, and interestingly, based on the recovery of TAGLN2 + G-actin in the F-actin fraction (Fig. 1a), addition of TAGLN2 to G-actin produced filamentous forms of actin under low-salt conditions in which actin polymerization is suppressed, suggesting that TAGLN2 may nucleate G-actin polymerization under low-salt conditions
To accomplish the above processes, actin cytoskeletons must be spatiotemporally regulated by the actin-binding proteins (ABPs) that account for approximately 25% of total cellular protein[36]
Summary
The TAGLN superfamily comprises TAGLN1, 2, and 3 isoforms, which have high degrees of sequence identity (~80%). TAGLN1 maintains the differentiated phenotype of vascular smooth muscle cells (VSMCs) by inducing filamentous actin bundling[9]. Only a few proteins can induce actin polymerization under low-salt conditions[11,12,13,14,15,16,17] This newly found characteristic of TAGLN2 led us to determine the actin-based properties of full-length TAGLN2 and its subdomains. TAGLN2 blocked the binding of the Arp2/3 complex to the actin filament under physiological salt conditions. These characteristics of TAGLN2 may be associated with its biological functions to induce filopodia-like phenotypes. We determined the localization and function of TAGLN2 in HeLa cells and human and mouse T cells, as these cells express considerable amounts of TAGLN2
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