TES-1/Tes and ZYX-1/Zyxin protect junctional actin networks under tension during epidermal morphogenesis in the C. elegans embryo.

LIM-domain-containing repeat (LCR) proteins are recruited to strained actin filaments within stress fibers in cultured cells, but their roles at cell-cell junctions in living organisms have not been extensively studied. Here, we show that the Caenorhabditis elegans LCR proteins TES-1/Tes and ZYX-1/Zyxin are recruited to apical junctions during embryonic elongation when junctions are under tension. In genetic backgrounds in which embryonic elongation fails, junctional recruitment is severely compromised.

A conserved phosphorylation switch controls the interaction between cadherin and β-catenin in vitro and in vivo.

In metazoan adherens junctions, β-catenin links the cytoplasmic tail of classical cadherins to the F-actin-binding protein α-catenin. Phosphorylation of a Ser/Thr-rich region in the cadherin tail dramatically enhances affinity for β-catenin and promotes cell-cell adhesion in cell culture systems, but its importance has not been demonstrated in vivo. Here, we identify a critical phosphorylated serine in the C.

Improved safety with intravenous insulin therapy for critically ill patients with renal failure.

Objective: The aim of this study was to evaluate the safety and efficacy of a new intravenous (IV) regular human insulin infusion (RHI) algorithm for glycemic control in critically ill patients with renal failure.

Methods: Adult trauma patients with renal failure who received a new RHI algorithm were compared with those who received the discontinued RHI algorithm (historical control). Target blood glucose (BG) concentration was 70 to 149 mg/dL (3.

Specific conserved C-terminal amino acids of Caenorhabditis elegans HMP-1/α-catenin modulate F-actin binding independently of vinculin.

Stable intercellular adhesions formed through the cadherin-catenin complex are important determinants of proper tissue architecture and help maintain tissue integrity during morphogenetic movements in developing embryos. A key regulator of this stability is α-catenin, which connects the cadherin-catenin complex to the actin cytoskeleton. Although the C-terminal F-actin-binding domain of α-catenin has been shown to be crucial for its function, a more detailed in vivo analysis of discrete regions and residues required for actin binding has not been performed.

A genome-wide functional screen shows MAGI-1 is an L1CAM-dependent stabilizer of apical junctions in C. elegans.

Background: In multicellular organisms, cell-cell junctions are involved in many aspects of tissue morphogenesis. α-catenin links the cadherin-catenin complex (CCC) to the actin cytoskeleton, stabilizing cadherin-dependent adhesions.

Results: To identify modulators of cadherin-based cell adhesion, we conducted a genome-wide RNAi screen in C.

Tropomodulin protects α-catenin-dependent junctional-actin networks under stress during epithelial morphogenesis.

α-catenin is central to recruitment of actin networks to the cadherin-catenin complex, but how such networks are subsequently stabilized against stress applied during morphogenesis is poorly understood. To identify proteins that functionally interact with α-catenin in this process, we performed enhancer screening using a weak allele of the C. elegans α-catenin, hmp-1, thereby identifying UNC-94/tropomodulin.

The F-BAR domain of SRGP-1 facilitates cell-cell adhesion during C. elegans morphogenesis.

Robust cell-cell adhesion is critical for tissue integrity and morphogenesis, yet little is known about the molecular mechanisms controlling cell-cell junction architecture and strength. We discovered that SRGP-1 is a novel component of cell-cell junctions in Caenorhabditis elegans, localizing via its F-BAR (Bin1, Amphiphysin, and RVS167) domain and a flanking 200-amino acid sequence. SRGP-1 activity promotes an increase in membrane dynamics at nascent cell-cell contacts and the rapid formation of new junctions; in addition, srgp-1 loss of function is lethal in embryos with compromised cadherin-catenin complexes.

In vitro and in vivo reconstitution of the cadherin-catenin-actin complex from Caenorhabditis elegans.

The ternary complex of cadherin, beta-catenin, and alpha-catenin regulates actin-dependent cell-cell adhesion. alpha-Catenin can bind beta-catenin and F-actin, but in mammals alpha-catenin either binds beta-catenin as a monomer or F-actin as a homodimer. It is not known if this conformational regulation of alpha-catenin is evolutionarily conserved.

SAX-7/L1CAM and HMR-1/cadherin function redundantly in blastomere compaction and non-muscle myosin accumulation during Caenorhabditis elegans gastrulation.

Gastrulation is the first major morphogenetic movement in development and requires dynamic regulation of cell adhesion and the cytoskeleton. Caenorhabditis elegans gastrulation begins with the migration of the two endodermal precursors, Ea and Ep, from the surface of the embryo into the interior. Ea/Ep migration provides a relatively simple system to examine the intersection of cell adhesion, cell signaling, and cell movement.

Identifying the molecular signature of the interstitial deletion 7q subgroup of uterine leiomyomata using a paired analysis.

Uterine leiomyomata (UL), the most common neoplasm in reproductive-age women, have recurrent cytogenetic abnormalities including interstitial deletion of 7q. To develop a molecular signature, matched del(7q) and non-del(7q) tumors identified by FISH or karyotyping from 11 women were profiled with expression arrays. Our analysis using paired t tests demonstrates this matched design is critical to eliminate the confounding effects of genotype and environment that underlie patient variation.

The assembly and maintenance of epithelial junctions in C. elegans.

The epithelial tissues of the C. elegans embryo provide a "minimalist" system for examining phylogenetically conserved proteins that function in epithelial polarity and cell-cell adhesion in a multicellular organism. In this review, we provide an overview of three major molecular complexes at the apical surface of epithelial cells in the C.

Dynamic analysis identifies novel roles for DLG-1 subdomains in AJM-1 recruitment and LET-413-dependent apical focusing.

Cell-cell junctions are composed of a diverse array of specialized proteins that are necessary for the movement and integrity of epithelia. Scaffolding molecules, such as membrane-associated guanylate kinases (MAGUKs) contain multiple protein-protein interaction domains that integrate these proteins into macromolecular complexes at junctions. We have used structure-function experiments to dissect the role of domains of the Caenorhabditis elegans MAGUK DLG-1, a homolog of Drosophila Discs large and vertebrate SAP97.

The impact of race as a risk factor for symptom severity and age at diagnosis of uterine leiomyomata among affected sisters.

Objective: The objective of the study was to identify risk factors for uterine leiomyomata (UL) in a racially diverse population of women with a family history of UL, and to evaluate their contribution to disease severity and age at diagnosis.

Study Design: We collected and analyzed epidemiologic data from 285 sister pairs diagnosed with UL. Risk factors for UL-related outcomes were compared among black (n = 73) and white (n = 212) sister pairs using univariate and multivariate regression models.