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elegans catenin

Remco A Mentink, Lorenzo Rella, Tomasz W Radaszkiewicz, Tomáš Gybel, Marco C Betist, Vitězslav Bryja, Hendrik C Korswagen
Van Gogh-like (Vangl) and Prickle (Pk) are core components of the non-canonical Wnt planar cell polarity pathway that controls epithelial polarity and cell migration. Studies in vertebrate model systems have suggested that Vangl and Pk may also inhibit signaling through the canonical Wnt/β-catenin pathway, but the functional significance of this potential cross-talk is unclear. In the nematode C. elegans, the Q neuroblasts and their descendants migrate in opposite directions along the anteroposterior body axis...
December 7, 2018: PLoS Genetics
Fiona Kerr, Ivana Bjedov, Oyinkan Sofola-Adesakin
Lithium has long been used for the treatment of psychiatric disorders, due to its robust beneficial effect as a mood stabilizing drug. Lithium's effectiveness for improving neurological function is therefore well-described, stimulating the investigation of its potential use in several neurodegenerative conditions including Alzheimer's (AD), Parkinson's (PD) and Huntington's (HD) diseases. A narrow therapeutic window for these effects, however, has led to concerted efforts to understand the molecular mechanisms of lithium action in the brain, in order to develop more selective treatments that harness its neuroprotective potential whilst limiting contraindications...
2018: Frontiers in Molecular Neuroscience
Wei Wei, Fei Jiang, Xiao-Chang Liu, Qian Su
Novel studies have shown that the Transmembrane protein 9 (TMEM9) gene is localized at 1q41 and encodes a protein consisting of 183 amino acids with an N-terminus containing many important domains. As a novel human transmembrane protein, TMEM9 is highly conserved in species from Caenorhabditis elegans to humans and is widely expressed in many tissues and cells. Moreover, TMEM9 may play an important role in intracellular transport and the growth of hepatoma cells. However, evidence for the function of TMEM9 in inflammation is still limited...
October 2018: International Immunopharmacology
Yanjun Shi, Qian Li, Zhiyong Shao
Synapses are specialized neuronal connections essential for neuronal function. Defects in synaptic assembly or maintenance usually lead to various neurological disorders. Synaptic assembly is regulated by secreted molecules such as Wnts. Wnts are a large family of conserved glycosylated signaling molecules involved in many aspects of neural development and maintenance. However, the molecular mechanisms by which Wnts regulate synaptic assembly remain elusive due to the large number of ligands/receptors, the diversity of signaling cascades and the complexity of the nervous system...
2018: Frontiers in Molecular Neuroscience
Thanh Thi Kim Vuong-Brender, Arthur Boutillon, David Rodriguez, Vincent Lavilley, Michel Labouesse
Adherens junctions (AJs) are key structures regulating tissue integrity and maintaining adhesion between cells. During morphogenesis, junctional proteins cooperate closely with the actomyosin network to drive cell movement and shape changes. How the junctions integrate the mechanical forces in space and in time during an in vivo morphogenetic event is still largely unknown, due to a lack of quantitative data. To address this issue, we inserted a functional Fluorescence Resonance Energy Transfer (FRET)-based force biosensor within HMP-1/α-catenin of Caenorhabditis elegans...
2018: PloS One
Guillaume Bordet, Vincent Bertrand
Transcription factors of the Zic family play important roles during animal development, and their misregulation has been implicated in several human diseases. Zic proteins are present in nematodes, and their function has been mostly studied in the model organism C. elegans. C. elegans possesses only one Zic family member, REF-2. Functional studies have shown that this factor plays a key role during the development of the nervous system, epidermis, and excretory system. In addition, they have revealed that the C...
2018: Advances in Experimental Medicine and Biology
Kenji Sugioka, Lars-Eric Fielmich, Kota Mizumoto, Bruce Bowerman, Sander van den Heuvel, Akatsuki Kimura, Hitoshi Sawa
The adenomatous polyposis coli (APC) tumor suppressor has dual functions in Wnt/β-catenin signaling and accurate chromosome segregation and is frequently mutated in colorectal cancers. Although APC contributes to proper cell division, the underlying mechanisms remain poorly understood. Here we show that Caenorhabditis elegans APR-1/APC is an attenuator of the pulling forces acting on the mitotic spindle. During asymmetric cell division of the C. elegans zygote, a LIN-5/NuMA protein complex localizes dynein to the cell cortex to generate pulling forces on astral microtubules that position the mitotic spindle...
January 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
Shashikala Sasidharan, Sofya Borinskaya, Falshruti Patel, Yelena Bernadskaya, Sailaja Mandalapu, Maria Agapito, Martha C Soto
Actin is an integral component of epithelial apical junctions, yet the interactions of branched actin regulators with apical junction components are still not clear. Biochemical data have shown that α-catenin inhibits Arp2/3-dependent branched actin. These results suggested that branched actin is only needed at earliest stages of apical junction development. We use live imaging in developing C. elegans embryos to test models for how WAVE-induced branched actin collaborates with other apical junction proteins during the essential process of junction formation and maturation...
February 1, 2018: Developmental Biology
Tony J C Harris
The scaffold protein Par-3 ( Drosophila Bazooka) is a central organizer of cell polarity across animals. This review focuses on how the clustering of Par-3 contributes to cell polarity. It begins with the Par-3 homo-oligomerization mechanism and its regulation by Par-1 phosphorylation. The role of polarized cytoskeletal networks in distributing Par-3 clusters to one end of the cell is then discussed, as is the subsequent maintenance of polarized Par-3 clusters through hindered mobility and inhibition from the opposite pole...
2017: F1000Research
Xiangqiang Shao, Hyunook Kang, Timothy Loveless, Gyu Rie Lee, Chaok Seok, William I Weis, Hee-Jung Choi, Jeff Hardin
Stable tissue integrity during embryonic development relies on the function of the cadherin·catenin complex (CCC). The Caenorhabditis elegans CCC is a useful paradigm for analyzing in vivo requirements for specific interactions among the core components of the CCC, and it provides a unique opportunity to examine evolutionarily conserved mechanisms that govern the interaction between α- and β-catenin. HMP-1, unlike its mammalian homolog α-catenin, is constitutively monomeric, and its binding affinity for HMP-2/β-catenin is higher than that of α-catenin for β-catenin...
October 6, 2017: Journal of Biological Chemistry
Myon-Hee Lee, Dong Suk Yoon
Stem cells have the ability to self-renew and to generate differentiated cell types. A regulatory network that controls this balance is critical for stem cell homeostasis and normal animal development. Particularly, Ras-ERK/MAPK signaling pathway is critical for stem cell self-renewal and differentiation in mammals, including humans. Aberrant regulation of Ras-ERK/MAPK signaling pathway results in either stem cell or overproliferation. Therefore, the identification of Ras-ERK/MAPK signaling pathway-associated regulators is critical to understand the mechanism of stem cell (possibly cancer stem cell) control...
2017: Methods in Molecular Biology
Arielle Koonyee Lam, Bryan T Phillips
Asymmetric cell division is a common mode of cell differentiation during the invariant lineage of the nematode, C. elegans. Beginning at the four-cell stage, and continuing throughout embryogenesis and larval development, mother cells are polarized by Wnt ligands, causing an asymmetric inheritance of key members of a Wnt/β-catenin signal transduction pathway termed the Wnt/β-catenin asymmetry pathway. The resulting daughter cells are distinct at birth with one daughter cell activating Wnt target gene expression via β-catenin activation of TCF, while the other daughter displays transcriptional repression of these target genes...
2017: Results and Problems in Cell Differentiation
Hyunook Kang, Injin Bang, Kyeong Sik Jin, Boyun Lee, Junho Lee, Xiangqiang Shao, Jonathon A Heier, Adam V Kwiatkowski, W James Nelson, Jeff Hardin, William I Weis, Hee-Jung Choi
Intercellular epithelial junctions formed by classical cadherins, β-catenin, and the actin-binding protein α-catenin link the actin cytoskeletons of adjacent cells into a structural continuum. These assemblies transmit forces through the tissue and respond to intracellular and extracellular signals. However, the mechanisms of junctional assembly and regulation are poorly understood. Studies of cadherin-catenin assembly in a number of metazoans have revealed both similarities and unexpected differences in the biochemical properties of the cadherin·catenin complex that likely reflect the developmental and environmental requirements of different tissues and organisms...
April 28, 2017: Journal of Biological Chemistry
Scott M Robertson, Jessica Medina, Marieke Oldenbroek, Rueyling Lin
The MS blastomere produces one-third of the body wall muscles (BWMs) in the C. elegans embryo. MS-derived BWMs require two distinct cell-cell interactions, the first inhibitory and the second, two cell cycles later, required to overcome this inhibition. The inductive interaction is not required if the inhibitory signal is absent. Although the Notch receptor GLP-1 was implicated in both interactions, the molecular nature of the two signals was unknown. We now show that zygotically expressed MOM-2 (Wnt) is responsible for both interactions...
February 1, 2017: Development
Nivedita Chatterjee, Youngho Kim, Jisu Yang, Carlos P Roca, Sang-Woo Joo, Jinhee Choi
The potential hazards of graphene nanomaterials were investigated by exposing the nematode Caenorhabditis elegans to graphene oxide (GO) and reduced graphene oxide (rGO). The underlying mechanisms of the nano-bio interaction were addressed with an integrated systems toxicology approach using global transcriptomics, network-based pathway analysis, and experimental validation of the in-silico-derived hypotheses. Graphene oxide was found to reduce the worms' reproductive health to a greater degree than rGO, but it did not affect survival (24 h endpoint)...
February 2017: Nanotoxicology
Sonnhild Mittag, Tomas Valenta, Jörg Weiske, Laura Bloch, Susanne Klingel, Dietmar Gradl, Franziska Wetzel, Yuan Chen, Iver Petersen, Konrad Basler, Otmar Huber
Nitrilase1 was classified as a tumour suppressor in association with the fragile histidine-triad protein Fhit. However, knowledge about nitrilase1 and its tumour suppressor function is still limited. Whereas nitrilase1 and Fhit are discrete proteins in mammals, they are merged in Drosophila melanogaster and Caenorhabditis elegans. According to the Rosetta-Stone hypothesis, proteins encoded as fusion proteins in one organism and as separate proteins in another organism may act in the same signalling pathway...
2016: Cell Discovery
Daniel J Marston, Christopher D Higgins, Kimberly A Peters, Timothy D Cupp, Daniel J Dickinson, Ariel M Pani, Regan P Moore, Amanda H Cox, Daniel P Kiehart, Bob Goldstein
Apical constriction is a change in cell shape that drives key morphogenetic events including gastrulation and neural tube formation. Apical force-producing actomyosin networks drive apical constriction by contracting while connected to cell-cell junctions. The mechanisms by which developmental patterning regulates these actomyosin networks and associated junctions with spatial precision are not fully understood. Here we identify a myosin light-chain kinase MRCK-1 as a key regulator of C. elegans gastrulation that integrates spatial and developmental patterning information...
August 22, 2016: Current Biology: CB
Vincent Bertrand
The Wnt/β-catenin pathway plays key roles during animal development. In several species, β-catenin is used in a reiterative manner to regulate cell fate diversification between daughter cells following division. This binary cell fate specification mechanism has been observed in animals that belong to very diverse phyla: the nematode Caenorhabditis elegans, the annelid Platynereis, and the ascidian Ciona. It may also play a role in the regulation of several stem cell lineages in vertebrates. While the molecular mechanism behind this binary cell fate switch is not fully understood, it appears that both secreted Wnt ligands and asymmetric cortical factors contribute to the generation of the difference in nuclear β-catenin levels between daughter cells...
May 2016: Wiley Interdisciplinary Reviews. Developmental Biology
Denise Wernike, Yun Chen, Karina Mastronardi, Neetha Makil, Alisa Piekny
Tissue morphogenesis requires myosin-dependent events such as cell shape changes and migration to be coordinated between cells within a tissue, and/or with cells from other tissues. However, few studies have investigated the simultaneous morphogenesis of multiple tissues in vivo. We found that during Caenorhabditis elegans ventral enclosure, when epidermal cells collectively migrate to cover the ventral surface of the embryo, the underlying neuroblasts (neuronal precursor cells) also undergo morphogenesis. We found that myosin accumulates as foci along the junction-free edges of the ventral epidermal cells to form a ring, whose closure is myosin-dependent...
April 15, 2016: Developmental Biology
Hyunook Kang, Injin Bang, William I Weis, Hee-Jung Choi
Adherens junctions transmit mechanical force between cells. In these junctions, β-catenin binds to cadherins and to the N-terminal domain of α-catenin, which in turn binds to actin filaments via its C-terminal domain. The middle (M) domain of α-catenin plays an important role in responding to mechanical tension. The nematode Caenorhabditis elegans contains α- and β-catenin homologues called HMP-1 and HMP-2, respectively, but HMP-1 behaves differently from its mammalian homologue. Thus, structural and biochemical studies of HMP-1 have been initiated to understand the mechanism of HMP-1 and the evolution of α-catenin...
March 2016: Acta Crystallographica. Section F, Structural Biology Communications
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