ABSTRACT
Vinculin is a cytoskeletal linker strengthening cell adhesion. The Shigella IpaA invasion effector binds to vinculin to promote vinculin supra-activation associated with head-domain-mediated oligomerization. Our study investigates the impact of mutations of vinculin D1D2 subdomains' residues predicted to interact with IpaA VBS3. These mutations affected the rate of D1D2 trimer formation with distinct effects on monomer disappearance, consistent with structural modeling of a closed and open D1D2 conformer induced by IpaA. Notably, mutations targeting the closed D1D2 conformer significantly reduced Shigella invasion of host cells as opposed to mutations targeting the open D1D2 conformer and later stages of vinculin head-domain oligomerization. In contrast, all mutations affected the formation of focal adhesions (FAs), supporting the involvement of vinculin supra-activation in this process. Our findings suggest that IpaA-induced vinculin supra-activation primarily reinforces matrix adhesion in infected cells, rather than promoting bacterial invasion. Consistently, shear stress studies pointed to a key role for IpaA-induced vinculin supra-activation in accelerating and strengthening cell-matrix adhesion.
Subject(s)
Cell Adhesion , Focal Adhesions , Vinculin , Vinculin/metabolism , Vinculin/genetics , Humans , Focal Adhesions/metabolism , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Mutation , Host-Pathogen Interactions , HeLa Cells , Protein Binding , Shigella/metabolism , Shigella/genetics , Antigens, Bacterial/metabolism , Antigens, Bacterial/genetics , Dysentery, Bacillary/microbiology , Dysentery, Bacillary/metabolismABSTRACT
Oroantral communication (OAC) is one of the main complications of extracting antral or sinus teeth. OAC is a gap between the maxillary sinus and the oral cavity. When left untreated, it causes maxillary sinusitis and dramatically impairs the patient's quality of life. Numerous surgical treatment techniques have been described, from mucosal techniques to using bone substitutes or very conservative alternative means. Many cases of recurrence after treatment have been reported, and the choice of the method adapted to the clinical situation remains challenging. Therefore, it is necessary to establish a correct diagnosis and choose the surgical technique best adapted to the case. This work is aimed at reviewing several techniques for the treatment of OAC and at describing our recommendations for use in daily practice for each of them through four clinical cases.
