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Journal of Cell Biology

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https://www.readbyqxmd.com/read/30242034/cell-polarity-and-adherens-junction-formation-inhibit-epithelial-fas-cell-death-receptor-signaling
#1
Laurent Gagnoux-Palacios, Hala Awina, Stéphane Audebert, Aurélie Rossin, Magali Mondin, Franck Borgese, Carlota Planas-Botey, Amel Mettouchi, Jean-Paul Borg, Anne-Odile Hueber
Finely tuned regulation of epithelial cell death maintains tissue integrity and homeostasis. At the cellular level, life and death decisions are controlled by environmental stimuli such as the activation of death receptors. We show that cell polarity and adherens junction formation prevent proapoptotic signals emanating from the Fas death receptor. Fas is sequestered in E-cadherin actin-based adhesion structures that are less able to induce downstream apoptosis signaling. Using a proteomic-based approach, we find that the polarity molecule Dlg1 interacts with the C-terminal PDZ-binding site in Fas and that this interaction decreases formation of the death-inducing complex upon engagement with Fas ligand (FasL), thus acting as an additional cell death protection mechanism...
September 21, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/30232100/emerging-mechanisms-of-asymmetric-stem-cell-division
#2
REVIEW
Zsolt G Venkei, Yukiko M Yamashita
The asymmetric cell division of stem cells, which produces one stem cell and one differentiating cell, has emerged as a mechanism to balance stem cell self-renewal and differentiation. Elaborate cellular mechanisms that orchestrate the processes required for asymmetric cell divisions are often shared between stem cells and other asymmetrically dividing cells. During asymmetric cell division, cells must establish asymmetry/polarity, which is guided by varying degrees of intrinsic versus extrinsic cues, and use intracellular machineries to divide in a desired orientation in the context of the asymmetry/polarity...
September 19, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/30228162/occluding-junctions-as-novel-regulators-of-tissue-mechanics-during-wound-repair
#3
Lara Carvalho, Pedro Patricio, Susana Ponte, Carl-Philipp Heisenberg, Luis Almeida, André S Nunes, Nuno A M Araújo, Antonio Jacinto
In epithelial tissues, cells tightly connect to each other through cell-cell junctions, but they also present the remarkable capacity of reorganizing themselves without compromising tissue integrity. Upon injury, simple epithelia efficiently resolve small lesions through the action of actin cytoskeleton contractile structures at the wound edge and cellular rearrangements. However, the underlying mechanisms and how they cooperate are still poorly understood. In this study, we combine live imaging and theoretical modeling to reveal a novel and indispensable role for occluding junctions (OJs) in this process...
September 18, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/30228161/cargo-regulates-clathrin-coated-pit-invagination-via-clathrin-light-chain-phosphorylation
#4
Hannes Maib, Filipe Ferreira, Stéphane Vassilopoulos, Elizabeth Smythe
Clathrin light chains (CLCs) control selective uptake of a range of G protein-coupled receptors (GPCRs), although the mechanism by which this occurs has remained elusive thus far. In particular, site-specific phosphorylation of CLCb controls the uptake of the purinergic GPCR P2Y12 , but it is dispensable for the constitutive uptake of the transferrin receptor (TfR). We demonstrate that phosphorylation of CLCb is required for the maturation of clathrin-coated pits (CCPs) through the transition of flat lattices into invaginated buds...
September 18, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/30228160/tatsushi-igaki-flying-up-the-research-summits
#5
Marie Anne O'Donnell
Igaki explores how cell-cell communication directs tissue and tumor development.
September 18, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/30217954/proteins-that-control-the-geometry-of-microtubules-at-the-ends-of-cilia
#6
Panagiota Louka, Krishna Kumar Vasudevan, Mayukh Guha, Ewa Joachimiak, Dorota Wloga, Raphaël F-X Tomasi, Charles N Baroud, Pascale Dupuis-Williams, Domenico F Galati, Chad G Pearson, Luke M Rice, James J Moresco, John R Yates, Yu-Yang Jiang, Karl Lechtreck, William Dentler, Jacek Gaertig
Cilia, essential motile and sensory organelles, have several compartments: the basal body, transition zone, and the middle and distal axoneme segments. The distal segment accommodates key functions, including cilium assembly and sensory activities. While the middle segment contains doublet microtubules (incomplete B-tubules fused to complete A-tubules), the distal segment contains only A-tubule extensions, and its existence requires coordination of microtubule length at the nanometer scale. We show that three conserved proteins, two of which are mutated in the ciliopathy Joubert syndrome, determine the geometry of the distal segment, by controlling the positions of specific microtubule ends...
September 14, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/30209069/the-kinetoplastid-kinetochore-protein-kkt4-is-an-unconventional-microtubule-tip-coupling-protein
#7
Aida Llauró, Hanako Hayashi, Megan E Bailey, Alex Wilson, Patryk Ludzia, Charles L Asbury, Bungo Akiyoshi
Kinetochores are multiprotein machines that drive chromosome segregation by maintaining persistent, load-bearing linkages between chromosomes and dynamic microtubule tips. Kinetochores in commonly studied eukaryotes bind microtubules through widely conserved components like the Ndc80 complex. However, in evolutionarily divergent kinetoplastid species such as Trypanosoma brucei , which causes sleeping sickness, the kinetochores assemble from a unique set of proteins lacking homology to any known microtubule-binding domains...
September 12, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/30209068/-xrp1-genetically-interacts-with-the-als-associated-fus-orthologue-caz-and-mediates-its-toxicity
#8
Moushami Mallik, Marica Catinozzi, Clemens B Hug, Li Zhang, Marina Wagner, Julia Bussmann, Jonas Bittern, Sina Mersmann, Christian Klämbt, Hannes C A Drexler, Martijn A Huynen, Juan M Vaquerizas, Erik Storkebaum
Cabeza ( caz ) is the single Drosophila melanogaster orthologue of the human FET proteins FUS, TAF15, and EWSR1, which have been implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. In this study, we identified Xrp1 , a nuclear chromatin-binding protein, as a key modifier of caz mutant phenotypes. Xrp1 expression was strongly up-regulated in caz mutants, and Xrp1 heterozygosity rescued their motor defects and life span. Interestingly, selective neuronal Xrp1 knockdown was sufficient to rescue, and neuronal Xrp1 overexpression phenocopied caz mutant phenotypes...
September 12, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/30206148/dendritic-actin-delivery-service
#9
Yun-Jin Pai, Adrian W Moore
The mechanisms by which the actin cytoskeleton regulates dendritic branching are not fully understood. Nithianandam and Chien (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201711136) discover actin blobs, new structures that mediate dynamic actin delivery within a growing dendrite arbor and that mark sites of future branch formation.
September 11, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/30194270/mechanical-principles-of-nuclear-shaping-and-positioning
#10
REVIEW
Tanmay P Lele, Richard B Dickinson, Gregg G Gundersen
Positioning and shaping the nucleus represents a mechanical challenge for the migrating cell because of its large size and resistance to deformation. Cells shape and position the nucleus by transmitting forces from the cytoskeleton onto the nuclear surface. This force transfer can occur through specialized linkages between the nuclear envelope and the cytoskeleton. In response, the nucleus can deform and/or it can move. Nuclear movement will occur when there is a net differential in mechanical force across the nucleus, while nuclear deformation will occur when mechanical forces overcome the mechanical resistance of the various structures that comprise the nucleus...
September 7, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/30194269/intronless-mrnas-transit-through-nuclear-speckles-to-gain-export-competence
#11
Ke Wang, Lantian Wang, Jianshu Wang, Suli Chen, Min Shi, Hong Cheng
Nuclear speckles (NSs) serve as splicing factor storage sites. In this study, we unexpectedly found that many endogenous intronless mRNAs, which do not undergo splicing, associate with NSs. These associations do not require transcription, polyadenylation, or the polyA tail. Rather, exonic splicing enhancers present in intronless mRNAs and their binding partners, SR proteins, promote intronless mRNA localization to NSs. Significantly, speckle targeting of mRNAs promotes the recruitment of the TREX export complex and their TREX-dependent nuclear export...
September 7, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/30194268/myoepithelial-crowd-control-of-cancer-cells
#12
Katharine Goodwin, Celeste M Nelson
Smooth muscle-like cells can actively remodel epithelia, a mechanism common across developing tissues. In this issue, new work from Sirka et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201802144) demonstrates a novel mechanism for tumor suppression by smooth muscle-like myoepithelial cells of the mammary gland.
September 7, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/30190286/cytomatrix-proteins-cast-and-elks-regulate-retinal-photoreceptor-development-and-maintenance
#13
Akari Hagiwara, Yosuke Kitahara, Chad Paul Grabner, Christian Vogl, Manabu Abe, Ryo Kitta, Keisuke Ohta, Keiichiro Nakamura, Kenji Sakimura, Tobias Moser, Akinori Nishi, Toshihisa Ohtsuka
At the presynaptic active zone (AZ), the related cytomatrix proteins CAST and ELKS organize the presynaptic release machinery. While CAST is known to regulate AZ size and neurotransmitter release, the role of ELKS and the integral system of CAST/ELKS together is poorly understood. Here, we show that CAST and ELKS have both redundant and unique roles in coordinating synaptic development, function, and maintenance of retinal photoreceptor ribbon synapses. A CAST/ELKS double knockout (dKO) mouse showed high levels of ectopic synapses and reduced responses to visual stimulation...
September 6, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/30185604/retrograde-regulation-of-mossy-fiber-axon-targeting-and-terminal-maturation-via-postsynaptic-lnx1
#14
Xian-Dong Liu, Xiao-Na Zhu, Michael M Halford, Tian-Le Xu, Mark Henkemeyer, Nan-Jie Xu
Neuronal connections are initiated by axon targeting to form synapses. However, how the maturation of axon terminals is modulated through interacting with postsynaptic elements remains elusive. In this study, we find that ligand of Numb protein X 1 (Lnx1), a postsynaptic PDZ protein expressed in hippocampal CA3 pyramidal neurons, is essential for mossy fiber (MF) axon targeting during the postnatal period. Lnx1 deletion causes defective synaptic arrangement that leads to aberrant presynaptic terminals. We further identify EphB receptors as novel Lnx1-binding proteins to form a multiprotein complex that is stabilized on the CA3 neuron membrane through preventing proteasome activity...
September 5, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/30181317/vps13-a-lipid-transfer-protein-making-contacts-at-multiple-cellular-locations
#15
Mingming Gao, Hongyuan Yang
The evolutionarily conserved VPS13 proteins localize to multiple membrane contact sites though their function and regulation has been elusive. Bean et al. (2018. J. Cell Biol. https://doi.org/10.1016/jcb.201804111) found that competitive adaptors control the different localizations of yeast Vps13p, while Kumar et al. (2018. J. Cell Biol. https://doi.org/10.1016/jcb.201807019) provide biochemical and structural evidence for VPS13 proteins in the nonvesicular transport of phospholipids.
September 4, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/30181316/interchromosomal-interactions-a-genomic-love-story-of-kissing-chromosomes
#16
REVIEW
Philipp G Maass, A Rasim Barutcu, John L Rinn
Nuclei require a precise three- and four-dimensional organization of DNA to establish cell-specific gene-expression programs. Underscoring the importance of DNA topology, alterations to the nuclear architecture can perturb gene expression and result in disease states. More recently, it has become clear that not only intrachromosomal interactions, but also interchromosomal interactions, a less studied feature of chromosomes, are required for proper physiological gene-expression programs. Here, we review recent studies with emerging insights into where and why cross-chromosomal communication is relevant...
September 4, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/30171044/nuclear-rupture-at-sites-of-high-curvature-compromises-retention-of-dna-repair-factors
#17
Yuntao Xia, Irena L Ivanovska, Kuangzheng Zhu, Lucas Smith, Jerome Irianto, Charlotte R Pfeifer, Cory M Alvey, Jiazheng Ji, Dazhen Liu, Sangkyun Cho, Rachel R Bennett, Andrea J Liu, Roger A Greenberg, Dennis E Discher
The nucleus is physically linked to the cytoskeleton, adhesions, and extracellular matrix-all of which sustain forces, but their relationships to DNA damage are obscure. We show that nuclear rupture with cytoplasmic mislocalization of multiple DNA repair factors correlates with high nuclear curvature imposed by an external probe or by cell attachment to either aligned collagen fibers or stiff matrix. Mislocalization is greatly enhanced by lamin A depletion, requires hours for nuclear reentry, and correlates with an increase in pan-nucleoplasmic foci of the DNA damage marker γH2AX...
August 31, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/30154188/pink1-parkin-link-inflammation-mitochondrial-stress-and-neurodegeneration
#18
Laura E Newman, Gerald S Shadel
What causes inflammation in age-related neurodegenerative diseases remains a mystery. Sliter et al. (2018. Nature https://doi.org/10.1038/s41586-018-0448-9) show that, when damaged mitochondria cannot be removed by mitophagy, stress from exercise or mitochondrial DNA mutations activates the proinflammatory cGAS-STING pathway that may contribute to Parkinson's disease.
August 28, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/30154187/cdt1-stabilizes-kinetochore-microtubule-attachments-via-an-aurora-b-kinase-dependent-mechanism
#19
Shivangi Agarwal, Kyle Paul Smith, Yizhuo Zhou, Aussie Suzuki, Richard J McKenney, Dileep Varma
Robust kinetochore-microtubule (kMT) attachment is critical for accurate chromosome segregation. G2/M-specific depletion of human Cdt1 that localizes to kinetochores in an Ndc80 complex-dependent manner leads to abnormal kMT attachments and mitotic arrest. This indicates an independent mitotic role for Cdt1 in addition to its prototypic function in DNA replication origin licensing. Here, we show that Cdt1 directly binds to microtubules (MTs). Endogenous or transiently expressed Cdt1 localizes to both mitotic spindle MTs and kinetochores...
August 28, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/30154186/mapping-3d-genome-organization-relative-to-nuclear-compartments-using-tsa-seq-as-a-cytological-ruler
#20
Yu Chen, Yang Zhang, Yuchuan Wang, Liguo Zhang, Eva K Brinkman, Stephen A Adam, Robert Goldman, Bas van Steensel, Jian Ma, Andrew S Belmont
While nuclear compartmentalization is an essential feature of three-dimensional genome organization, no genomic method exists for measuring chromosome distances to defined nuclear structures. In this study, we describe TSA-Seq, a new mapping method capable of providing a "cytological ruler" for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling. Ensemble-averaged results in K562 cells reveal a clear nuclear lamina to speckle axis correlated with a striking spatial gradient in genome activity...
August 28, 2018: Journal of Cell Biology
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