Paumet Research

Highlighted Publications

G. Cingolani, M. McCauley, A. Lobley, A. Bryer, J. Wesolowski, R. Lokareddy, E. Ronzone, J. Perilla, F. Paumet An intramolecular clamp controls the fusogenic activity of a chlamydial SNARE-like protein”, Nature Communications (2019) 10: 2747 https://www.nature.com/articles/s41467-019-10806-9

This study presents the atomic structure of the cytoplasmic domain of IncA, which reveals a non-canonical four-helix bundle. Structure-based mutagenesis, molecular dynamics simulation, and functional cellular assays identify an intramolecular clamp that is essential for IncA-mediated homotypic membrane fusion during infection.

T. Monteiro-Bras, J. Wesolowski, F. Paumet Depletion of SNAP-23 and Syntaxin4 alters lipid droplet homeostasis during Chlamydia infection”, Microbial Cell (2019) 7:46-58. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993123/

This study demonstrates that the loss of SNAP23 and Syntaxin4 results in the dysregulation of Chlamydia-induced lipid droplets, indicating that both of these SNAREs play a critical role in lipid droplet homeostasis during Chlamydia infection. Ultimately, our data highlights the importance of lipid droplets and their regulation in Chlamydia development.

J. Wesolowski, MM. Weber, A. Nawrotek, CA. Dooley, M. Calderon, CM. St. Croix, T. Hackstadt, J. Cherfils, F. Paumet (2017) Chlamydia Hijacks ARF GTPases To Coordinate Microtubule Posttranslational Modifications and Golgi Complex Positioning” mBio 8: e02280-16

This study provides the first evidence that a chlamydial protein CT813 recruits the GTPases ARF1 and ARF4, which in turn play a critical role in controlling post-translationally modified microtubules around the inclusion. Furthermore, this study demonstrates that Chlamydia trachomatis hijacks this novel function of ARF to reposition the Golgi mini stacks during infection.

E. Ronzone, J Wesolowski, Laura D. Bauler, Anshul Bhardwaj, Ted Hackstadt, F. Paumet (2014)An alpha-helical core encodes the dual functions of the chlamydial protein IncA” Journal of Biological Chemistry, 289

Here, the functional core of the SNARE-like protein IncA has been identified, which provides the basis for a more comprehensive understanding of its mechanisms of action and could aid in the development of novel therapeutics capable of interfering with its pathogenic function in vivo. This project provides the most detailed understanding of how a chlamydial inclusion protein operates to manipulate membrane fusion.

J. Wesolowski, F. Paumet (2014) Escherichia coli exposure inhibits exocytic SNARE-mediated membrane fusion in mast cellsTraffic 15:516-530

This study demonstrates that E. coli exposure inhibits the formation of the exocytic SNARE complex and thus the release of granules. As a result, IgE-induced inflammatory reactions are significantly dampened. Ultimately, these results suggest that the microenvironment within which mast cells reside modulates their activation.

Recent Publications

Specialized contact sites regulate the fusion of chlamydial inclusion membranes

Chlamydia trachomatis Subverts Alpha-Actinins To Stabilize Its Inclusion

Cross Talk between ARF1 and RhoA Coordinates the Formation of Cytoskeletal Scaffolds during Chlamydia Infection

Depletion of SNAP-23 and Syntaxin 4 alters lipid droplet homeostasis during Chlamydia infection

Structural basis for the homotypic fusion of chlamydial inclusions by the SNARE-like protein IncA

Chlamydia hijacks ARF GTPases to coordinate microtubule posttranslational modifications and golgi complex positioning

Taking control: Reorganization of the host cytoskeleton by Chlamydia

A functional core of IncA is required for Chlamydia trachomatis inclusion fusion

An α-helical core encodes the dual functions of the chlamydial protein IncA

Extracellular traps are associated with human and mouse neutrophil and macrophage mediated killing of larval Strongyloides stercoralis

Escherichia coli exposure inhibits exocytic SNARE-mediated membrane fusion in mast cells

Two Coiled-Coil Domains of Chlamydia trachomatis IncA Affect Membrane Fusion Events during Infection

A Novel Function for SNAP29 (Synaptosomal-Associated Protein of 29 kDa) in Mast Cell Phagocytosis

The impact of bacterial infection on mast cell degranulation

SNARE motif: A common motif used by pathogens to manipulate membrane fusion

Intracellular bacteria encode inhibitory SNARE-like proteins

SNARE protein mimicry by an intracellular bacterium

Selective Activation of Cognate SNAREpins by Sec1/Munc18 Proteins

Concerted auto-regulation in yeast endosomal t-SNAREs

The specificity of SNARE-dependent fusion encoded in the SNARE motif

i-SNAREs: Inhibitory SNAREs that fine-tune the specificity of membrane fusion

Cell fusion

SNAREs and associated regulators in the control of exocytosis in the RBL-2H3 mast cell line

Mechanisms of membrane fusion

A t-SNARE of the endocytic pathway must be activated for fusion