Membrane-dependent actin polymerization mediated by the Legionella pneumophila effector protein MavH
Qing Zhang1,2, Min Wan1,2, Yuxin Mao1,2
1Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA.
Abstract:
L. pneumophila propagates in eukaryotic cells within a specialized niche, the Legionella -containing vacuole (LCV). The infection process is controlled by over 330 effector proteins delivered through the type IV secretion system. In this study, we report that the Legionella MavH effector harbors a lipid-binding domain that specifically recognizes PI(3)P (phosphatidylinositol 3-phosphate) and localizes to endosomes when ectopically expressed. We show that MavH recruits host actin capping proteins (CP) and actin to the endosome via its CP interacting (CPI) motif and WH2-like actin-binding domain, respectively. In vitro assays revealed that MavH stimulates robust actin polymerization only in the presence of PI(3)P-containing liposomes and the recruitment of CP by MavH negatively regulates F-actin density at the membrane. Furthermore, in L. pneumophila -infected cells, MavH can be detected around the LCV at the very early stage of infection. Together, our results reveal a novel mechanism of membrane-dependent actin polymerization catalyzed by MavH that may play a role at the early stage of L. pneumophila infection by regulating host actin dynamics.
Insights
Legionella MavH effector protein binds to PI(3)P and recruits host actin, influencing actin polymerization at the early stages of Legionella infection.
Area of Science:
- Microbiology
- Cell Biology
- Biochemistry
Background:
- Legionella pneumophila is an intracellular pathogen that replicates within a specialized vacuole (LCV).
- Over 330 effector proteins are secreted by L. pneumophila to manipulate host cell processes.
- Understanding effector protein function is crucial for deciphering bacterial pathogenesis.
Approach:
- Investigated the function of the L. pneumophila MavH effector protein.
- Characterized MavH's lipid-binding domain and its interaction with phosphatidylinositol 3-phosphate (PI(3)P).
- Assessed MavH's ability to recruit host actin and actin-binding proteins in vitro and in infected cells.
Key Points:
- MavH possesses a lipid-binding domain that specifically recognizes PI(3)P.
- MavH recruits host actin capping proteins (CP) and actin to endosomes via its CPI motif and WH2-like domain.
- MavH-mediated actin polymerization is dependent on PI(3)P and negatively regulated by CP recruitment.
Conclusions:
- MavH utilizes a novel mechanism of membrane-dependent actin polymerization.
- This process may regulate host actin dynamics during the early stages of L. pneumophila infection.
- MavH's function provides insights into bacterial strategies for manipulating host cell actin.
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