Vinculin and Rab5 Complex Is Requited for Uptake of Staphyrococcus aureus and Interleukin-6 Expression

Abstract

Vinculin, a 116-kDa membrane cytoskeletal protein, is an important molecule for cell adhesion; however, little is known about its other cellular functions. Here, we demonstrated that vinculin binds to Rab5 and is required for Staphylococcus aureus (S. aureus) uptake in cells. Viunculin directly bound to Rab5 and enhanced the activation of S. aureus uptake. Over-expression of active vinculin mutants enhanced S. aureus uptake, whereas over-expression of an inactive vinculin mutant decreased S. aureus uptake. Vinculin bound to Rab5 at the N-terminal region (1-258) of vinculin. Vinculin and Rab5 were involved in the S. aureus-induced phosphorylation of MAP kinases (p38, Erk, and JNK) and IL-6 expression. Finally, vinculin and Rab5 knockdown reduced infection of S. aureus, phosphorylation of MAPKs and IL-6 expression in murine lungs. Our results suggest that vinculin binds to Rab5 and that these two molecules cooperatively enhance bacterial infection and the inflammatory response.

Low-intensity pulsed ultrasound promotes cell motility through vinculin-controlled Rac1 GTPase activity

“…Rab5 is a GTPase that regulates endocytosis, previously shown to associate vinculin (Hagiwara et al, 2014;Mendoza et al, 2013); Rab5-positive vesicles also act as platforms for Rac1 trafficking to promote CDR formation (Lanzetti et al, 2004;Palamidessi et al, 2008). Since our results demonstrate that LIPUS promotes the formation of both endosomes and CDRs, we hypothesized that Rac1 activation after LIPUS stimulation may require Rab5.…”

“…The same study demonstrated that cell migration promotes the formation of a complex of Rab5 with β1 integrin, FAK, paxillin and vinculin, and that FAs are enriched with GTP-bound Rab5 (Mendoza et al, 2013). Furthermore, associations between β1 integrin and Rab5 (Pellinen et al, 2006), and vinculin and Rab5 (Hagiwara et al, 2014), have been observed, pertinent to our findings that Rac1 activation requires both vinculin and Rab5, and that vinculin appears to regulate the behaviour and morphology of Rab5-positive vesicles ( Fig. 7G,H; Movie 4).…”

Integration of “Omics” Strategies for Biomarkers Discovery and for the Elucidation of Molecular Mechanisms Underlying Brugada Syndrome

“…VNC is able to affect the expression of interleukin 6 whose upregulation might be determinant for the upregulation of Fibrinogen gamma chain, alpha‐2‐macroglobulin, complement C3, and miR 342–3p …”

Insights into endosomal maturation of human holo-transferrin in the enteric parasiteEntamoeba histolytica: essential roles of Rab7A and Rab5 in biogenesis of giant early endocytic vacuoles

“…Amoebic Rab5, like its human homologue, participates in the early phase of transferrin endocytosis (Fig. A and D) (Bucci et al ., ; Schnatwinkel et al ., ; Leclerc et al ., ; Hagiwara et al ., ). In contrast, Rab7A, the closest Rab7 isotype to its human homologue, showed significant deviation in terms of localization and role in intracellular trafficking.…”