Topological balance of cell distributions in plane monolayers.

Most of normal proliferative epithelia of plants and metazoans are topologically invariant and characterized by similar cell distributions according to the number of cell neighbors (DCNs). Here we study peculiarities of these distributions and explain why the DCN obtained from the location of intercellular boundaries and that based on the Voronoi tessellation with nodes located on cell nuclei may differ from each other. As we demonstrate, special microdomains where four or more intercellular boundaries converge are topologically charged.

The secreted tyrosine phosphatase PtpA promotes survival in RAW 264.7 macrophages through decrease of the SUMOylation host response.

uses numerous strategies to survive and persist in the intracellular environment of professional phagocytes, including modulation of the SUMOylation process. This study aims to understand how alters host SUMOylation to enhance its intracellular survival in professional phagocytes. Our results indicate that strain Newman utilizes PtpA-driven phosphorylation to decrease the amount of SUMOylated proteins in murine macrophages to facilitate its survival in this immune cell type.

A Mycobacterium tuberculosis Effector Targets Mitochondrion, Controls Energy Metabolism, and Limits Cytochrome Exit.

Host metabolism reprogramming is a key feature of Mycobacterium tuberculosis () infection that enables the survival of this pathogen within phagocytic cells and modulates the immune response facilitating the spread of the tuberculosis disease. Here, we demonstrate that a previously uncharacterized secreted protein from , Rv1813c, manipulates the host metabolism by targeting mitochondria. When expressed in eukaryotic cells, the protein is delivered to the mitochondrial intermembrane space and promotes the enhancement of host ATP production by boosting the oxidative phosphorylation metabolic pathway.

Ethnic differences in cellular and humoral immune responses to SARS-CoV-2 vaccination in UK healthcare workers: a cross-sectional analysis.

Background: Few studies have compared SARS-CoV-2 vaccine immunogenicity by ethnic group. We sought to establish whether cellular and humoral immune responses to SARS-CoV-2 vaccination differ according to ethnicity in UK Healthcare workers (HCWs).

Methods: In this cross-sectional analysis, we used baseline data from two immunological cohort studies conducted in HCWs in Leicester, UK.

Characterization of the Secreted Acid Phosphatase SapS Reveals a Novel Virulence Factor of That Contributes to Survival and Virulence in Mice.

possesses a large arsenal of immune-modulating factors, enabling it to bypass the immune system's response. Here, we demonstrate that the acid phosphatase SapS is secreted during macrophage infection and promotes its intracellular survival in this type of immune cell. In animal models, the SA564 mutant demonstrated a significantly lower bacterial burden in liver and renal tissues of mice at four days post infection in comparison to the wild type, along with lower pathogenicity in a zebrafish infection model.

Random nature of epithelial cancer cell monolayers.

Although the polygonal shape of epithelial cells has been drawing the attention of scientists for several centuries, only a decade and a half ago it was demonstrated that distributions of polygon types (DOPTs) are similar in proliferative epithelia of many different plant and animal species. In this study, we show that hyper-proliferation of cancer cells disrupts this universal paradigm and results in randomly organized epithelial structures. Examining non-synchronized and synchronized HeLa cervix cells, we suppose that the spread of cell sizes is the main parameter controlling the DOPT in the cancer cell monolayers.

The secreted protein kinase CstK from influences vacuole development and interacts with the GTPase-activating host protein TBC1D5.

The intracellular bacterial pathogen is the etiological agent of the emerging zoonosis Q fever. Crucial to its pathogenesis is type 4b secretion system-mediated secretion of bacterial effectors into host cells that subvert host cell membrane trafficking, leading to the biogenesis of a parasitophorous vacuole for intracellular replication. The characterization of prokaryotic serine/threonine protein kinases in bacterial pathogens is emerging as an important strategy to better understand host-pathogen interactions.

Ca-activated cleavage of ezrin visualised dynamically in living myeloid cells during cell surface area expansion.

The intracellular events underlying phagocytosis, a crucial event for innate immunity, are still unresolved. In order to test whether the reservoir of membrane required for the formation of the phagocytic pseudopodia is maintained by cortical ezrin, and that its cleavage is a key step in releasing this membrane, the cleavage of cortical ezrin was monitored within living phagocytes (the phagocytically competent cell line RAW264.7) through expressing two ezrin constructs with fluorescent protein tags located either inside the FERM or at the actin-binding domains.

Acetylation of translationally controlled tumor protein promotes its degradation through chaperone-mediated autophagy.

Translationally controlled tumor protein (Tpt1/TCTP) is a multi-functional cytosolic protein whose cellular levels are finely tuned. TCTP regulates protein behavior by favoring stabilization of protein partners or on the contrary by promoting degradation of others. TCTP has been shown to be transcriptionally and translationally regulated, but much less is known about its degradation process.

Enhancer of zeste acts as a major developmental regulator of Ciona intestinalis embryogenesis.

The paradigm of developmental regulation by Polycomb group (PcG) proteins posits that they maintain silencing outside the spatial expression domains of their target genes, particularly of Hox genes, starting from mid embryogenesis. The Enhancer of zeste [E(z)] PcG protein is the catalytic subunit of the PRC2 complex, which silences its targets via deposition of the H3K27me3 mark. Here, we studied the ascidian Ciona intestinalis counterpart of E(z).

Ezrin promotes actin assembly at the phagosome membrane and regulates phago-lysosomal fusion.

Phagosome maturation is defined as the process by which phagosomes fuse sequentially with endosomes and lysosomes to acquire an acidic pH and hydrolases that degrade ingested particles. While the essential role of actin cytoskeleton remodeling during particle internalization is well established, its role during the later stages of phagosome maturation remains largely unknown. We have previously shown that purified mature phagosomes assemble F-actin at their membrane, and that the ezrin-radixin-moesin (ERM) proteins ezrin and moesin participate in this process.

Differential roles of PtdIns(4,5)P2 and phosphorylation in moesin activation during Drosophila development.

The ezrin, radixin and moesin (ERM) proteins regulate cell membrane architecture in several cellular contexts. Current models propose that ERM activation requires a PtdIns(4,5)P(2)-induced conformational change, followed by phosphorylation of a conserved threonine. However, how these inputs contribute in vivo to orchestrate ERM activation is poorly understood.

Exosomal sorting of the cytoplasmic domain of bovine leukemia virus TM Env protein.

Exosomes are small membrane vesicles that are released into the extracellular compartment as a consequence of fusion of multivesicular endosomes with the plasma membrane. To unravel the molecular basis of protein sorting into exosomes, we have made a chimeric protein containing the cytosolic domain of the transmembrane subunit of the viral Env protein of BLV and the ectodomain of CD8 (CDTM-BLV-CD8). When expressed in K562 cells known to constitutively secrete exosomes, the chimera was found to be very efficiently targeted to the released vesicles.

DCC regulates cell adhesion in human colon cancer derived HT-29 cells and associates with ezrin.

The deleted in colorectal cancer (DCC) gene encodes a 170- to 190-kDa protein of the Immunoglobulin superfamily. Firstly identified as a tumor suppressor gene in human colorectal carcinomas, the main function for DCC has been described in the nervous system as part of a receptor complex for netrin-1. Moreover, roles in mucosecretory cell differentiation and as inducer of apoptosis have also been reported.

Delta-promoted filopodia mediate long-range lateral inhibition in Drosophila.

Drosophila thoracic mechanosensory bristles originate from cells that are singled out from 'proneural' groups of competent epithelial cells. Neural competence is restricted to individual sensory organ precursors (SOPs) by Delta/Notch-mediated 'lateral inhibition', whereas other cells in the proneural field adopt an epidermal fate. The precursors of the large macrochaetes differentiate separately from individual proneural clusters that comprise about 20-30 cells or as heterochronic pairs from groups of more than 100 cells, whereas the precursors of the small regularly spaced microchaetes emerge from even larger proneural fields.

Membrane targeting of protein tyrosine phosphatase PTPL1 through its FERM domain via binding to phosphatidylinositol 4,5-biphosphate.

PTPL1 is the largest known cytoplasmic protein tyrosine phosphatase (PTP) containing a FERM (four point-1, ezrin, radixin and moesin) domain. Enzyme localization and PTP-substrate specificity are thought to play crucial roles in the regulation of PTP activity, which determines their functions. Here we report that PTPL1 is predominantly localized at the apical face of plasma membrane enriched in dorsal microvilli when expressed in HeLa cells.

Molecular analysis of microscopic ezrin dynamics by two-photon FRAP.

Ezrin plays a key role in coupling signal transduction to cortical cell organization. This actin-membrane linker undergoes a series of conformational changes that modulate its interactions with various partners and its localization in membrane or cytosolic pools. Its mobility and exchange rates within and between these two pools were assessed by two-photon fluorescence recovery after photobleaching in epithelial cell microvilli.

Overexpression and structural study of the cathelicidin motif of the protegrin-3 precursor.

Numerous precursors of antibacterial peptides with unrelated sequences share a similar prosequence of 96-101 residues, referred to as the cathelicidin motif. The structure of this widespread motif has not yet been reported. The cathelicidin motif of protegrin-3 (ProS) was overexpressed in Escherichia coli as a His-tagged protein to facilitate its purification.