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Journal of Cell Science

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https://www.readbyqxmd.com/read/28818997/ccr2-3-utr-functions-as-a-competing-endogenous-rna-to-inhibit-breast-cancer-metastasis
#1
Jinhang Hu, Xiaoman Li, Xinwei Guo, Qianqian Guo, Chenxi Xiang, Zhiting Zhang, Yingying Xing, Tao Xi, Lufeng Zheng
Diverse RNA transcripts acting as competing endogenous RNAs (ceRNAs) can co-regulate each other's expression by competing for shared microRNAs. CCR2 protein, the receptor of CCL2, is implicated in cancer progression. However, our results showed that higher CCR2 mRNA level was remarkably associated with prolonged survival of breast cancer patients. The conflicting results prompt us to study the non-coding function of CCR2 mRNA. We indicated that CCR2 3'UTR inhibited MDA-MB-231 and MCF-7 cells metastasis by repressing EMT in vitro and suppressed breast cancer metastasis in vivo Mechanistically, CCR2 3'UTR modulated RhoGAP protein STARD13 expression via acting as a STARD13 ceRNA in a microRNA-dependent and protein coding-independent manner...
August 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28818996/regulation-of-cx37-channel-and-growth-suppressive-properties-by-phosphorylation
#2
Nicole L Jacobsen, Tasha K Pontifex, Hanjun Li, Joell L Solan, Paul D Lampe, Paul L Sorgen, Janis M Burt
Connexin 37 (Cx37)-mediated growth suppression requires interaction between its carboxyl terminus (CT) and functional pore-forming domain. Using rat insulinoma cells, we show that Cx37 induces cell death and cell cycle arrest as well as slowed cell cycling. Whether differential phosphorylation might regulate intramolecular interactions and consequently growth suppressive phenotype is unknown. Protein kinase C inhibition increased the open probability of low conductance gap junction channels (GJCh) and reduced GJCh closed state probability...
August 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28818995/maternal-dcaf2-is-crucial-for-maintenance-of-genome-stability-during-the-first-cell-cycle-in-mice
#3
Yi-Wen Xu, Lan-Rui Cao, Min Wang, Ying Xu, Xin Wu, Junping Liu, Chao Tong, Heng-Yu Fan
Precise regulation of DNA replication and genome integrity is crucial for gametogenesis and early embryogenesis. Cullin ring-finger ubiquitin ligase 4 (CRL4) has multiple functions in the maintenance of germ cell survival, oocyte meiotic maturation, and maternal-zygotic transition in mammals. DDB1-cullin 4-associated factor-2 (DCAF2, also known as DTL or CDT2) is an evolutionarily conserved substrate receptor of CRL4. To determine whether DCAF2 is a key CRL4 substrate adaptor in mammalian oocytes, we generated a novel mouse strain that carries a Dcaf2 allele flanked by LoxP sequences, and specifically deleted Dcaf2 in oocytes...
August 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28808090/the-wisdom-of-crowds-regulating-cell-function-through-condensed-states-of-living-matter
#4
REVIEW
Simon Alberti
Our understanding of cells has progressed rapidly in recent years, mainly because of technological advances. Modern technology now allows us to observe molecular processes in living cells with high spatial and temporal resolution. At the same time, we are beginning to compile the molecular parts list of cells. However, how all these parts work together to yield complex cellular behavior is still unclear. In addition, the established paradigm of molecular biology, which sees proteins as well-folded enzymes that undergo specific lock-and-key type interactions, is increasingly being challenged...
August 14, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28808089/bag3-mediated-proteostasis-at-a-glance
#5
REVIEW
Christina Klimek, Barbara Kathage, Judith Wördehoff, Jörg Höhfeld
Cellular and organismal survival depend on the ability to maintain the proteome, even under conditions that threaten protein integrity. BCL2-associated athanogene 3 (BAG3) is essential for protein homeostasis (proteostasis) in stressed cells. Owing to its multi-domain structure, it engages in diverse processes that are crucial for proteome maintenance. BAG3 promotes the activity of molecular chaperones, sequesters and concentrates misfolded proteins, initiates autophagic disposal, and balances transcription, translation and degradation...
August 14, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28808088/the-armadillo-protein-p0071-controls-kif3-motor-transport
#6
Alexander Becher, Tim Eiseler, Marc Porzner, Paul Walther, René Keil, Susanne Bobrovich, Mechthild Hatzfeld, Thomas Seufferlein
We here report a novel function of the armadillo protein p0071 during KIF3/kinesin-2-mediated transport. Secretion of chromogranin A and matrix metallopeptidase 9 from pancreatic neuroendocrine tumor cells or pancreatic cancer cells, respectively, was substantially reduced following knockdown of p0071. Vesicle tracking indicated impaired directional persistence of vesicles upon p0071 depletion. This suggests a disturbed balance between plus- and minus-end directed microtubule transport in cells lacking p0071...
August 14, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28808087/the-drosophila-lc8-homologue-cut-up-specifies-the-axonal-transport-of-proteasomes
#7
Tabita Kreko-Pierce, Benjamin A Eaton
Because of their functional polarity and elongated morphologies, microtubule-based transport of proteins and organelles is critical for normal neuronal function. The proteasome is required throughout the neuron for the highly regulated degradation of a broad set of protein targets whose functions underlie key physiological responses including synaptic plasticity and axonal degeneration. Molecularly, the relationship between proteasome transport and the transport of the targets of proteasomes is unclear. The dynein motor complex is required for the microtubule-based motility of numerous proteins and organelles in neurons...
August 14, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28808086/a-pharmacological-study-of-arabidopsis-cell-fusion-between-the-persistent-synergid-and-endosperm
#8
Kazuki Motomura, Tomokazu Kawashima, Frédéric Berger, Tetsu Kinoshita, Tetsuya Higashiyama, Daisuke Maruyama
Cell fusion is a pivotal process in fertilization and multinucleate cell formation. A plant cell is ubiquitously surrounded by hard cell wall, and very few cell fusions have been observed except for gamete fusions. We recently reported that the fertilized central cell (the endosperm) absorbs the persistent synergid, a highly differentiated cell necessary for pollen tube attraction. The synergid-endosperm fusion (SE fusion) appears to eliminate the persistent synergid from fertilized ovule in Arabidopsis thaliana Here, we analyzed the effects of various inhibitors on SE fusion by an in vitro-culture system...
August 14, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28808085/sub-mitochondrial-localization-of-genetic-tagged-mib-interacting-partners-mic19-mic60-and-sam50
#9
Mira Sastri, Manjula Darshi, Mason Mackey, Ranjan Ramachandra, Saeyeon Ju, Sebastien Phan, Stephen Adams, Kathryn Stein, Christopher R Douglas, Jiwan John Kim, Mark H Ellisman, Susan S Taylor, Guy A Perkins
Each mitochondrial compartment contains varying protein compositions that underlie a diversity of localized functions. Insights into the localization of mitochondrial intermembrane space bridging (MIB) components will have an impact on our understanding of mitochondrial architecture, dynamics and function. Using the novel visualizable genetic tags miniSOG and APEX2 in cultured mouse cardiac and human astrocyte cell lines and electron tomography, we have mapped at nanoscale resolution three key MIB components: Mic19, Mic60 and Sam50, in the environment of structural landmarks such as cristae and crista junctions (CJs)...
August 14, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28794017/differential-recruitment-of-e3-ubiquitin-ligase-complexes-regulates-ret-isoform-internalization
#10
Brandy D Hyndman, Mathieu J F Crupi, Susan Peng, Leslie N Bone, Aisha N Rekab, Eric Y Lian, Simona M Wagner, Costin N Antonescu, Lois M Mulligan
The RET receptor tyrosine kinase is implicated in normal development and cancer. RET is expressed as two isoforms, RET9 and RET51, with unique C-terminal tail sequences that recruit distinct protein complexes to mediate signals. Upon activation, RET isoforms are internalized with distinct kinetics, suggesting differences in regulation. Here, we demonstrate that RET9 and RET51 differ in their abilities to recruit E3-ubiquitin ligases to their unique C-termini. RET51, but not RET9, interacts with, and is ubiquitinated by CBL, which is recruited through interactions with the GRB2 adaptor protein...
August 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28794016/serine-protease-inhibitor-serpinb2-binds-and-stabilizes-p21-in-senescent-cells
#11
Hsi-Hsien Hsieh, Ying-Chieh Chen, Jing-Ru Jhan, Jing-Jer Lin
SerpinB2 is a serine protease inhibitor that is also known as plasminogen activator inhibitor type 2 (PAI-2). It has been well documented that SerpinB2 is an inhibitor of urokinase plasminogen activator (uPA) and tissue plasminogen activator (tPA). Interestingly, SerpinB2 level is increased in senescent cells and is considered a senescence biomarker. Through mimicking the elevated level of SerpinB2 in senescent cells, this study showed the proliferating human fibroblasts were induced into senescence. Senescence induced by SerpinB2 did not relate to its extracellular function as inhibition of SerpinB2 secretion, exogenous introduced SerpinB2, or a SerpinB2 mutant that failed to bind to its extracellular target uPA, did not have an effect on senescence...
August 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28794015/the-deubiquitylating-enzyme-ubp12-regulates-rad23-dependent-proteasomal-degradation
#12
Daniela Gödderz, Tatiana Álvarez Giovannucci, Jana Laláková, Victoria Menéndez Benito, Nico P Dantuma
The consecutive actions of the ubiquitin-selective segregase Cdc48 and the ubiquitin shuttle factor Rad23 result in the delivery of ubiquitylated proteins at the proteasome. Here, we show that the deubiquitylating enzyme Ubp12 interacts with Cdc48 and regulates proteasomal degradation of Rad23-dependent substrates. Overexpression of Ubp12 results in stabilization of Rad23-dependent substrates. We show that Ubp12 removes short ubiquitin chains from the N-terminal ubiquitin-like domain (UbL) of Rad23. Preventing ubiquitylation of Rad23 by substitution of lysine residues within the UbL domain, Rad23(UbLK0), does not affect the non-proteolytic role of Rad23 in DNA repair but causes an increase in ubiquitylated cargo bound to the UBA2 domains of Rad23 and recapitulates the stabilization of Rad23-dependent substrates observed upon overexpression of Ubp12...
August 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28794014/iron-affects-ire1-clustering-propensity-and-the-amplitude-of-endoplasmic-reticulum-stress-signaling
#13
Nir Cohen, Michal Breker, Anush Bakunts, Kristina Pesek, Ainara Chas, Josepmaria Argemí, Andrea Orsi, Lihi Gal, Silvia Chuartzman, Yoav Wigelman, Felix Jonas, Peter Walter, Robert Ernst, Tomás Aragón, Eelco van Anken, Maya Schuldiner
The unfolded protein response (UPR) allows cells to adjust secretory pathway capacity according to need. Ire1, the endoplasmic reticulum (ER) stress sensor and central activator of the UPR is conserved from the budding yeast Saccharomyces cerevisiae to humans. Under ER stress conditions, Ire1 clusters into foci that enable optimal UPR activation. To discover factors that affect Ire1 clustering, we performed a high-content screen using a whole-genome yeast mutant library expressing Ire1-mCherry. We imaged the strains following UPR induction and found 154 strains that displayed alterations in Ire1 clustering...
August 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28794013/control-mechanisms-in-germ-cells-mediated-by-p53-family-proteins
#14
REVIEW
Jakob Gebel, Marcel Tuppi, Katharina Krauskopf, Daniel Coutandin, Susanne Pitzius, Sebastian Kehrloesser, Christian Osterburg, Volker Dötsch
Germ cells are totipotent and, in principle, immortal as they are the source for new germ cells in each generation. This very special role requires tight quality control systems. The p53 protein family constitutes one of the most important quality surveillance systems in cells. Whereas p53 has become famous for its role as the guardian of the genome in its function as the most important somatic tumor suppressor, p63 has been nicknamed 'guardian of the female germ line'. p63 is strongly expressed in resting oocytes and responsible for eliminating those that carry DNA double-strand breaks...
August 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28778988/calcium-coordination-controls-sonic-hedgehog-structure-and-scube2-cubulin-domain-regulated-release
#15
Petra Jakobs, Philipp Schulz, Sabine Schürmann, Stephan Niland, Sebastian Exner, Rocio Rebollido-Rios, Dominique Manikowski, Daniel Hoffmann, Daniela G Seidler, Kay Grobe
Proteolytic processing of cell-surface bound ligands, called shedding, is a fundamental system to control cell-cell signaling. Yet, our understanding of how shedding is regulated is still incomplete. One way to increase the processing of dual-lipidated membrane-associated Sonic hedgehog (Shh) is to increase the density of substrate and sheddase. This releases and also activates Shh by the removal of lipidated inhibitory N-terminal peptides from their receptor binding sites. Shh release and activation is enhanced by Scube2 [signal sequence, cubulin (CUB) domain, epidermal growth factor (EGF)-like protein 2], raising the question of how this is achieved...
August 4, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28778987/the-f-actin-binding-rapgef-gflb-is-required-for-efficient-macropinocytosis-in-dictyostelium
#16
Hironori Inaba, Koji Yoda, Hiroyuki Adachi
Macropinocytosis involves the uptake of large volumes of fluid, which is regulated by various small GTPases. The Dictyostelium discoideum protein GflB is a guanine nucleotide exchange factor (GEF) of Rap1, involved in chemotaxis. Here we studied the role of GflB in macropinocytosis, phagocytosis, and cytokinesis. In plate culture of vegetative cells, compared with the parental strain AX2, gflB KO cells were flatter and more polarized, whereas GflB-overproducing cells were rounder. The gflB KO cells exhibited impaired crown formation and retraction, particularly retraction, resulting in more crowns (macropinocytic cups) per cell and longer crown lifetimes...
August 4, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28778986/a-gef-activity-independent-function-for-nuclear-net1-in-nodal-smad2-signal-transduction-and-mesendoderm-formation
#17
Shi Wei, Guozhu Ning, Linwei Li, Yifang Yan, Shuyan Yang, Yu Cao, Qiang Wang
Net1 is a well-characterized oncoprotein with RhoA-specific GEF activity. Oncogenic Net1 lacking the first 145 amino acids is present in the cytosol and contributes to the efficient activation of RhoA and the formation of actin stress fibers in a number of tumor cell types. Meanwhile, wild-type Net1 is predominantly localized in the nucleus at steady state due to its N-terminal nuclear localization sequences, where the function of nuclear Net1 has not been fully determined. Here, we find that zebrafish net1 is expressed specifically in mesendoderm precursors during gastrulation...
August 4, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28775156/the-sharpin-interactome-reveals-a-role-for-sharpin-in-lamellipodium-formation-via-the-arp2-3-complex
#18
Meraj H Khan, Siiri I Salomaa, Guillaume Jacquemet, Umar Butt, Mitro Miihkinen, Takahiro Deguchi, Elena Kremneva, Pekka Lappalainen, Martin J Humphries, Jeroen Pouwels
Sharpin, a multifunctional adaptor protein, regulates several signalling pathways. For example, Sharpin enhances signal-induced NF-κB signalling as part of the linear ubiquitin assembly complex (LUBAC) and inhibits integrins, the T cell receptor, caspase1 and PTEN. However, despite recent insights into Sharpin and LUBAC function, a systematic approach to identify signalling pathways regulated by Sharpin has not been reported. Here, we present the first 'Sharpin interactome', which identifies a large amount of novel potential Sharpin interactors in addition to several known ones...
August 3, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28775155/peroxisomal-plant-metabolism-an-update-on-nitric-oxide-ca-2-and-the-nadph-recycling-network
#19
REVIEW
Francisco J Corpas, Juan B Barroso
Plant peroxisomes are recognized organelles that - with their capacity to generate greater amounts of H2O2 than other subcellular compartments - have a remarkable oxidative metabolism. However, over the last 15 years, new information has shown that plant peroxisomes contain other important molecules and enzymes, including nitric oxide (NO), peroxynitrite, a NADPH-recycling system, Ca(2+) and lipid-derived signals, such as jasmonic acid (JA) and nitro-fatty acid (NO2-FA). This highlights the potential for complex interactions within the peroxisomal nitro-oxidative metabolism, which also affects the status of the cell and consequently its physiological processes...
August 3, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28775154/a-genome-wide-crispr-screen-reconciles-the-role-of-n-linked-glycosylation-in-galectin-3-transport-to-the-cell-surface
#20
Sarah E Stewart, Sam A Menzies, Stephanie J Popa, Natalia Savinykh, Anna Petrunkina Harrison, Paul J Lehner, Kevin Moreau
Galectins are a family of lectin binding proteins expressed both intracellularly and extracellularly. Galectin-3 (Gal-3) is expressed at the cell surface, however, Gal-3 lacks a signal sequence and the mechanism of Gal-3 transport to the cell surface remain poorly understood. Here, using a genome-wide CRISPR/Cas9 forward genetic screen for regulators of Gal-3 cell surface localization we identified genes encoding glycoproteins, enzymes involved in N-linked glycosylation, regulators of ER-Golgi trafficking and proteins involved in immunity...
August 3, 2017: Journal of Cell Science
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