Paumet Research

C. Linton, J. Wesolowski, K. Hanada, T. Yamaji, A. Lobley, F. Paumet “Specialized contact sites regulate the fusion of chlamydial inclusion membranes”, Nature Communications (2024), 15: 9250        https://www.nature.com/articles/s41467-024-53443-7

This study reveals that inclusions form unique contact sites (ICSs) prior to fusion, which serve as fusogenic platforms in which specific lipids and chlamydial proteins concentrate. In fact, fusion depends on the clustering of the chlamydial protein IncA within ICSs and is regulated by PI(3,4)P₂ and sphingolipids. As IncA concentrates within ICSs, its C-terminus interacts in trans with IncA on the apposing membrane, securing a high concentration of IncA at fusion sites, and initiating fusion.

A. Haines, J. Wesolowski, Ryan, N, T. Monteiro-Bras, F. Paumet “Cross-talk between ARF and RhoA coordinates the formation of actin and microtubule cytoskeletal scaffolds during Chlamydia infection” mBio (2021) 12: e02397-21.     https://journals.asm.org/doi/10.1128/mbio.02397-21

Chlamydia weaves an extensive network of microtubules (MTs) and actin filaments around the inclusion to enhance its stability and enable interactions with organelles. This study demonstrates how the chlamydial protein InaC relies on crosstalk between ARF1 and RhoA to coordinate MTs and actin, in which RhoA downregulates stable MT scaffolds, and ARF1 activation inhibits actin scaffolds. Understanding how Chlamydia hijacks complex networks will help elucidate how this clinically significant pathogen parasitizes its host and reveal novel cellular signaling pathways.

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.

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    https://journals.asm.org/doi/10.1128/mbio.02280-16

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.