Dynamin-dependent entry of Chlamydia trachomatis is sequentially regulated by the effectors TarP and TmeA.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 Jun 2024
10 Jun 2024
Historique:
received:
21
09
2023
accepted:
30
05
2024
medline:
11
6
2024
pubmed:
11
6
2024
entrez:
10
6
2024
Statut:
epublish
Résumé
Chlamydia invasion of epithelial cells is a pathogen-driven process involving two functionally distinct effectors - TarP and TmeA. They collaborate to promote robust actin dynamics at sites of entry. Here, we extend studies on the molecular mechanism of invasion by implicating the host GTPase dynamin 2 (Dyn2) in the completion of pathogen uptake. Importantly, Dyn2 function is modulated by TarP and TmeA at the levels of recruitment and activation through oligomerization, respectively. TarP-dependent recruitment requires phosphatidylinositol 3-kinase and the small GTPase Rac1, while TmeA has a post-recruitment role related to Dyn2 oligomerization. This is based on the rescue of invasion duration and efficiency in the absence of TmeA by the Dyn2 oligomer-stabilizing small molecule activator Ryngo 1-23. Notably, Dyn2 also regulated turnover of TarP- and TmeA-associated actin networks, with disrupted Dyn2 function resulting in aberrant turnover dynamics, thus establishing the interdependent functional relationship between Dyn2 and the effectors TarP and TmeA.
Identifiants
pubmed: 38858371
doi: 10.1038/s41467-024-49350-6
pii: 10.1038/s41467-024-49350-6
doi:
Substances chimiques
Dynamin II
EC 3.6.5.5
Actins
0
rac1 GTP-Binding Protein
EC 3.6.5.2
Bacterial Proteins
0
RAC1 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4926Subventions
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : AI065545
Informations de copyright
© 2024. The Author(s).
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