A Legionella Effector Disrupts Host Cytoskeletal Structure by Cleaving Actin
Yao Liu1, Wenhan Zhu1, Yunhao Tan1
1Purdue Institute for Inflammation, Immunology and Infectious Diseases and Department of Biological Sciences, Purdue University, West Lafayette, IN, United States of America.
Plos Pathogens
|January 28, 2017
Summary
Legionella pneumophila uses the RavK effector to cleave actin, disrupting host cell structure. This mechanism is crucial for bacterial colonization and survival within host cells during infection.
Area of Science:
- Microbiology
- Cell Biology
- Biochemistry
Background:
- Legionella pneumophila causes Legionnaires' disease by replicating within host cells.
- The Dot/Icm type IVB secretion system is essential for L. pneumophila pathogenesis, delivering ~300 effector proteins.
- Host cell modulation is critical for pathogen survival and replication.
Purpose of the Study:
- Identify novel Dot/Icm substrates.
- Investigate the function of RavK, a Dot/Icm substrate.
- Determine the mechanism by which RavK affects host cells.
Main Methods:
- Ectopic expression of RavK in mammalian cells.
- Biochemical assays to identify RavK's target and cleavage site.
- Site-directed mutagenesis to assess RavK function.
- Microscopy to observe cellular effects.
Main Results:
- RavK targets the host cytoskeleton, reducing actin filament abundance.
- RavK possesses metalloprotease activity (H95EXXH99 motif) essential for its function.
- RavK directly cleaves actin between Thr351 and Phe352, preventing polymerization.
- Actin cleavage by RavK occurs during L. pneumophila infection.
- A non-cleavable actin mutant (F352A) rescues RavK-induced cell rounding.
Conclusions:
- RavK is a novel L. pneumophila effector that cleaves host actin.
- Actin cytoskeleton manipulation is a key strategy for L. pneumophila intracellular replication.
- L. pneumophila utilizes multiple effectors to control host cell processes, particularly actin dynamics.
Related Concept Videos
01:19Actin Filament Depolymerization
4.1K
Actin filaments (F-actin) are composed of actin subunits. The dissociation of actin monomers can occur from either end of F-actin. The rate of dissociation is faster from the minus-end or the pointed end, where the actin subunits exist with a bound ADP, together known as ADP-actin. The depolymerization of F-actin is aided by proteins, including the actin-depolymerizing factor (ADF) and cofilin family of proteins, gelsolin, and glia maturation factor (GMF).
In F-actin, the ADF/cofilin proteins...
In F-actin, the ADF/cofilin proteins...
4.1K
01:39Mechanism of Filopodia Formation
3.3K
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
3.3K
01:35Disassembly of Intermediate Filaments
2.8K
Intermediate filaments (IFs) do not undergo spontaneous disassembly. Enzymes, kinases, and phosphatases add and remove phosphates from specific sites to regulate their disassembly. The IF concentration in the cytoplasm also regulates the disassembly. If the concentration crosses a threshold, it activates the protein kinases in the vicinity, allowing the phosphorylation of IFs.
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
2.8K
01:13Actin Polymerization and Cell Motility
7.0K
Actin is a family of globular proteins that are highly abundant in eukaryotic cells. It makes up approximately 1-5% of total cell protein concentration. Actin monomers polymerize to form a complex network of polarized filaments, the actin cytoskeleton, that plays a crucial role in many cellular processes, including cell motility, division, endocytosis, and metastasis of cancer cells.
Actin cytoskeleton dynamics can produce pushing, pulling, and resistance forces that help the cell to migrate....
Actin cytoskeleton dynamics can produce pushing, pulling, and resistance forces that help the cell to migrate....
7.0K
01:11Formation of Higher-order Actin Filaments
3.7K
The polymerization of G-actin monomers into filamentous F-actin is a multi-step process. Once the F-actins are formed, they can bundle together in different arrangements to form higher-order networks and regulate cellular functions. Common examples include the formation of lamellipodia and filopodia at the cell's leading edge by actin reorganization in a migrating cell. The microvilli on the brush border epithelial cells are also formed through the F-actin network.
The high-order actin...
The high-order actin...
3.7K
01:14Generation of Straight or Branched Actin Filaments
3.9K
The straight or branched structure formation of actin filaments is controlled by nucleating proteins such as the formins and Arp2/3 complex. Formin-mediated assembly results in straight filaments, whereas Arp2/3 protein complex-mediated assembly results in branched actin filaments.
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
3.9K