Ezrin and CD44 participate in the internalization process of Coxiella burnetii into non‐phagocytic cells. (31st July 2022)

• Record Type: Journal Article
• Authors: Distel, Jesús S.; Ortiz Flores, Rodolfo M.; Bienvenu, Arthur; Aguilera, Milton O.; Bonazzi, Matteo; Berón, Walter
• Is Part Of: Biology of the cell. Volume 114:Number 9(2022)
• Page Start: 237
• Page End: 253
• Publication Date: 2022-07-31
• Subjects: Coxiella burnetii -- CD44 -- Ezrin -- phagocytosis; Cytology -- Periodicals; Electron microscopy -- Periodicals; 571.6
• DOI: 10.1111/boc.202100096
• Languages: English
• ISSNs: 0248-4900

Abstract

Abstract: Ezrin protein is involved in the interaction of actin cytoskeleton with membrane receptors such as CD44. It regulates plasma membrane dynamics and intracellular signaling. Coxiella burnetii, the etiologic agent of Q fever, is internalized into host cell through a poorly characterized molecular mechanism. Here we analyzed the role of ezrin and CD44 in the C. burnetii internalization by HeLa cells. The knockdown of ezrin and CD44 inhibited the bacterial uptake. Interestingly, at early stages of C. burnetii internalization, ezrin was recruited to the cell membrane fraction and phosphorylated. Moreover, the overexpression of non‐phosphorylatable and phosphomimetic ezrin mutants decreased and increased the bacterial entry, respectively. A decrease in the internalization of C. burnetii was observed by the overexpression of CD44 truncated forms containing the intracellular or the extracellular domains. Interestingly, the CD44 mutant was unable to interact with ERM proteins decreased the bacterial internalization. These findings demonstrate the participation of ezrin in the internalization process of C. burnetii in non‐phagocytic cells. Additionally, we present evidence that CD44 receptor would be involved in that process. Abstract : In this work, we demonstrated that Ezrin, a membrane‐cytoskeleton linker, and CD44, a cell surface adhesion receptor, play an important role in the internalization of C. burnetii by epithelial cells. We show that C. burnetii uptake was significantly inhibited by the knockdown or non‐functional mutant overexpression of these proteins. During infection, Ezrin activation was evidenced by its recruitment to the plasma membrane and phosphorylation. We suggested that ROCK is implicated in the phosphorylation of Ezrin during C. burnetii internalization.