Transgelin-2 mimics bacterial SipA and promotes membrane ruffling and phagocytosis in lipopolysaccharide-activated macrophages

Abstract

Abstract Some bacteria utilize their secreted proteins to induce massive actin polymerization at the site of invasion in host cells. Salmonella protein SipA polymerizes host actin under low ionic conditions, where it is usually completely suppressed, and induces membrane ruffling as an infection mechanism. However, no protein that possesses SipA function has been identified in eukaryotic cells. We show here that transgelin-2 – which reveals a similar function to SipA in vitro – is dramatically induced in macrophages in response to lipopolysaccharide via partially the NF-κB pathways. Transgelin-2 intensively localizes at the actin-rich membrane ruffles during fMLP stimulation. Interestingly, macrophages with trangelin-2 deficiency (TAGLN2−/−) reveal a dramatic reduction of membrane ruffles with attenuated membrane dynamics, resulting in retarded phagocytic functions. Collectively, these results suggest that host macrophages have evolved to utilize the same mechanism of bacterial infection to engulf invaded bacteria.