Swiprosin-1 Is a Novel Actin Bundling Protein That Regulates Cell Spreading and Migration

Abstract

Protein functions are often revealed by their localization to specialized cellular sites. Recent reports demonstrated that swiprosin-1 is found together with actin and actin-binding proteins in the cytoskeleton fraction of human mast cells and NK-like cells. However, direct evidence of whether swiprosin-1 regulates actin dynamics is currently lacking. We found that swiprosin-1 localizes to microvilli-like membrane protrusions and lamellipodia and exhibits actin-binding activity. Overexpression of swiprosin-1 enhanced lamellipodia formation and cell spreading. In contrast, swiprosin-1 knockdown showed reduced cell spreading and migration. Swiprosin-1 induced actin bundling in the presence of Ca2+, and deletion of the EF-hand motifs partially reduced bundling activity. Swiprosin-1 dimerized in the presence of Ca2+ via its coiled-coil domain, and a lysine (Lys)-rich region in the coiled-coil domain was essential for regulation of actin bundling. Consistent with these observations, mutations of the EF-hand motifs and coiled-coil region significantly reduced cell spreading and lamellipodia formation. We provide new evidence of how swiprosin-1 influences cytoskeleton reorganization and cell spreading.

Swiprosin-1 deficiency impairs macrophage immune response of septic mice

“…Swiprosin-1 has been reported to affect cell migration by remodeling the actin cytoskeleton (26)(27)(28). Our results showed that swiprosin-1 deletion restrained macrophage recruitment, which partly explained the attenuated proinflammatory cytokine production in the local tissues.…”

Swiprosin-1 Promotes Mitochondria-Dependent Apoptosis of Glomerular Podocytes via P38 MAPK Pathway in Early-Stage Diabetic Nephropathy

“…Previous studies [17, 20, 21] showed that swiprosin-1 was widely accumulated in tissues such as the spleen, lung, liver, heart, and brain in particular. Swiprosin-1 was also expressed in immune cells such as human and primary murine mast cells [14], murine B cells, T cells [15-17], macrophages, natural killer cells [18, 19], and human peripheral blood mononuclear cells [20].…”

“…Swiprosin-1 was also expressed in immune cells such as human and primary murine mast cells [14], murine B cells, T cells [15-17], macrophages, natural killer cells [18, 19], and human peripheral blood mononuclear cells [20]. Protein atlas database indicates that swiprosin-1 is moderately expressed in human renal glomeruli but not tubules (http://www.proteinatlas.org/ENSG00000142634-$EFHD2/tissue/kidney#imid_13574299), which is consistent with the finidng of the present study that swiprosin-1 was moderately expressed in podocytes of renal glomeruli.…”

“…Swiprosin-1, also known as EF hand domain containing 2 (EFhd2), was initially identified as a novel protein in human CD8 + lymphocytes [14], and subsequently in immature, resting or activated B cells [15-17], macrophages and natural killer cells [18, 19], and non-lymphoid tissues such as the brain, spleen, lung, liver and heart [17, 20, 21]. In murine B cells, ectopic expression of swiprosin-1 was found to enhance spontaneous and B-cell receptor induced apoptosis [16, 22].…”

The Adaptor Protein Swiprosin-1/EFhd2 Is Dispensable for Platelet Function in Mice

“…EFhd2 has been proposed to play a crucial role in these processes in different cell types [18]. To test this in platelets, Efhd2 -/- and wild-type platelets were allowed to spread on a fibrinogen-coated surface in the presence of low concentrations of thrombin (Figure 4 A).…”