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Extraction of High Molecular Weight DNA from Microbial Mats
Published on: July 7, 2011
Virus Infection Triggers MAVS Polymers of Distinct Molecular Weight
Natalia Zamorano Cuervo1, Quentin Osseman2,3, Nathalie Grandvaux4,5
1CRCHUM-Centre Hospitalier de l'Université de Montréal, 900 rue Saint Denis, Montréal, QC H2X 0A9, Canada. Natalia.zamorano@umontreal.ca.
Abstract:
The mitochondrial antiviral signaling (MAVS) adaptor protein is a central signaling hub required for cells to mount an antiviral response following virus sensing by retinoic acid-inducible gene I (RIG-I)-like receptors. MAVS localizes in the membrane of mitochondria and peroxisomes and in mitochondrial-associated endoplasmic reticulum membranes. Structural and functional studies have revealed that MAVS activity relies on the formation of functional high molecular weight prion-like aggregates. The formation of protein aggregates typically relies on a dynamic transition between oligomerization and aggregation states. The existence of intermediate state(s) of MAVS polymers, other than aggregates, has not yet been documented. Here, we used a combination of non-reducing SDS-PAGE and semi-denaturing detergent agarose gel electrophoresis (SDD-AGE) to resolve whole cell extract preparations to distinguish MAVS polymerization states. While SDD-AGE analysis of whole cell extracts revealed the formation of previously described high molecular weight prion-like aggregates upon constitutively active RIG-I ectopic expression and virus infection, non-reducing SDS-PAGE allowed us to demonstrate the induction of lower molecular weight oligomers. Cleavage of MAVS using the NS3/4A protease revealed that anchoring to intracellular membranes is required for the appropriate polymerization into active high molecular weight aggregates. Altogether, our data suggest that RIG-I-dependent MAVS activation involves the coexistence of MAVS polymers with distinct molecular weights.
Insights
The mitochondrial antiviral signaling (MAVS) protein forms distinct polymer states, including lower molecular weight oligomers and high molecular weight aggregates, during antiviral responses. Membrane anchoring is crucial for MAVS polymerization into active aggregates.
Area of Science:
- Immunology
- Cell Biology
- Virology
Background:
- Mitochondrial antiviral signaling (MAVS) is essential for cellular antiviral immunity, acting downstream of RIG-I-like receptor sensing.
- MAVS functions as a signaling hub, localizing to mitochondrial, peroxisomal, and ER membranes.
- MAVS activity depends on prion-like aggregation, but intermediate polymerization states remain poorly understood.
Purpose of the Study:
- To investigate the distinct polymerization states of MAVS during antiviral signaling.
- To characterize the role of membrane anchoring in MAVS aggregate formation.
- To elucidate the dynamics of MAVS polymerization beyond high molecular weight aggregates.
Main Methods:
- Utilized non-reducing SDS-PAGE and semi-denaturing detergent agarose gel electrophoresis (SDD-AGE) to analyze MAVS polymerization.
- Examined MAVS polymerization states in whole cell extracts under conditions of RIG-I activation and viral infection.
- Assessed the impact of MAVS cleavage by NS3/4A protease on polymerization.
Main Results:
- SDD-AGE confirmed the formation of high molecular weight MAVS aggregates upon RIG-I activation and infection.
- Non-reducing SDS-PAGE revealed the induction of lower molecular weight MAVS oligomers.
- MAVS cleavage demonstrated that membrane anchoring is necessary for the formation of active high molecular weight aggregates.
Conclusions:
- RIG-I-dependent MAVS activation involves a spectrum of MAVS polymers, including both oligomers and aggregates.
- The study identifies distinct MAVS polymerization states, expanding the understanding of its signaling mechanism.
- Membrane association is critical for the proper assembly of functional MAVS aggregates in antiviral immunity.
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