Ezrin and CD44 participate in the internalization process of Coxiella burnetii into non-phagocytic cells.

Biol Cell

Instituto de Histología y Embriología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo - CONICET, Mendoza, Argentina.

Published: September 2022

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.

Download full-text PDF

Source
http://dx.doi.org/10.1111/boc.202100096DOI Listing

Publication Analysis

Top Keywords

ezrin cd44
12
internalization process
8
coxiella burnetii
8
burnetii non-phagocytic
8
non-phagocytic cells
8
burnetii internalization
8
ezrin
7
internalization
6
burnetii
6
cd44
6

Similar Publications

Despite extensive research, strategies to effectively combat breast cancer stemness and achieve a definitive cure remains elusive. CD44, a well-defined cancer stem cell (CSC) marker is reported to promote breast cancer tumorigenesis, metastasis, and chemoresistance. However, mechanisms leading to its enhanced expression and function is poorly understood.

View Article and Find Full Text PDF

Redistribution of the glycocalyx exposes phagocytic determinants on apoptotic cells.

Dev Cell

April 2024

Program in Cell Biology, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address:

Phagocytes remove dead and dying cells by engaging "eat-me" ligands such as phosphatidylserine (PtdSer) on the surface of apoptotic targets. However, PtdSer is obscured by the bulky exofacial glycocalyx, which also exposes ligands that activate "don't-eat-me" receptors such as Siglecs. Clearly, unshielding the juxtamembrane "eat-me" ligands is required for the successful engulfment of apoptotic cells, but the mechanisms underlying this process have not been described.

View Article and Find Full Text PDF

Microscopic clusters feature the composition of biochemical tetraspanin-assemblies and constitute building-blocks of tetraspanin enriched domains.

Sci Rep

January 2024

Faculty of Mathematics and Natural Sciences, Life & Medical Sciences (LIMES) Institute, University of Bonn, Carl-Troll-Straße 31, 53115, Bonn, Germany.

Biochemical approaches revealed that tetraspanins are multi-regulatory proteins forming a web, where they act in tetraspanin-enriched-microdomains (TEMs). A microscopic criterion differentiating between web and TEMs is lacking. Using super-resolution microcopy, we identify co-assemblies between the tetraspanins CD9 and CD81 and CD151 and CD81.

View Article and Find Full Text PDF

Discovery of FERM domain protein-protein interaction inhibitors for MSN and CD44 as a potential therapeutic approach for Alzheimer's disease.

J Biol Chem

December 2023

Alzheimer's Research UK Oxford Drug Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine Research Building, University of Oxford, Oxford, UK. Electronic address:

Proteomic studies have identified moesin (MSN), a protein containing a four-point-one, ezrin, radixin, moesin (FERM) domain, and the receptor CD44 as hub proteins found within a coexpression module strongly linked to Alzheimer's disease (AD) traits and microglia. These proteins are more abundant in Alzheimer's patient brains, and their levels are positively correlated with cognitive decline, amyloid plaque deposition, and neurofibrillary tangle burden. The MSN FERM domain interacts with the phospholipid phosphatidylinositol 4,5-bisphosphate (PIP) and the cytoplasmic tail of CD44.

View Article and Find Full Text PDF

Despite the advancements in targeted therapy for BRAFV600E-mutated metastatic colorectal cancer (mCRC), the development of resistance to BRAFV600E inhibition limits the response rate and durability of the treatment. Better understanding of the resistance mechanisms to BRAF inhibitors will facilitate the design of novel pharmacological strategies for BRAF-mutated mCRC. The aim of this study was to identify novel protein candidates involved in acquired resistance to BRAFV600E inhibitor vemurafenib in BRAFV600E-mutated colon cancer cells using an integrated proteomics approach.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!