Rho-dependent membrane folding causes Shigella entry into epithelial cells

Area of Science:

• Cell biology
• Microbiology
• Molecular biology

Background:

• The small GTPase Rho is essential for cytoskeletal organization, including stress fibers and focal adhesions.
• Shigella bacteria invade host cells by inducing a unique membrane structure.

Purpose of the Study:

• To investigate the role of the small GTPase Rho in Shigella-induced membrane remodeling during bacterial entry into HeLa cells.
• To elucidate the specific Rho isoforms involved and their function in the invasion process.

Main Methods:

• Utilized live-cell imaging and immunofluorescence to observe Rho isoform recruitment to bacterial entry sites.
• Employed a Rho-specific inhibitor to assess its impact on membrane folding and bacterial invasion.
• Applied S1-myosin labeling to analyze Rho's effect on actin dynamics (polymerization and nucleation).

Main Results:

• Shigella-induced membrane folding during bacterial entry is dependent on the small GTPase Rho.
• Differential recruitment of Rho isoforms to the bacterial entry site was observed.
• Inhibition of Rho abolished Shigella-induced membrane folding and impaired bacterial invasion.
• Rho mediated Shigella-induced actin polymerization, but not nucleation, at the invasion site.

Conclusions:

• The small GTPase Rho is a key regulator of cytoskeletal rearrangements necessary for Shigella invasion.
• Rho acts downstream of actin nucleation, promoting actin polymerization essential for host cell entry.
• This study identifies a critical signaling link between bacterial pathogens and host cell machinery for invasion.