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Journal of Cell Biology

Takahide Matsui, Peidu Jiang, Saori Nakano, Yuriko Sakamaki, Hayashi Yamamoto, Noboru Mizushima
Macroautophagy is an evolutionarily conserved catabolic mechanism that delivers intracellular constituents to lysosomes using autophagosomes. To achieve degradation, lysosomes must fuse with closed autophagosomes. We previously reported that the soluble N -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein syntaxin (STX) 17 translocates to autophagosomes to mediate fusion with lysosomes. In this study, we report an additional mechanism. We found that autophagosome-lysosome fusion is retained to some extent even in STX17 knockout (KO) HeLa cells...
May 22, 2018: Journal of Cell Biology
ShiHui Wang, ChenYu Wu, YueBin Zhang, QingLu Zhong, Hao Sun, WenPeng Cao, GaoXiang Ge, GuoHui Li, X Frank Zhang, JianFeng Chen
Chemokine (C-C motif) ligand 25 (CCL25) and C-X-C motif chemokine 10 (CXCL10) induce the ligand-specific activation of integrin α4β7 to mediate the selective adhesion of lymphocytes to mucosal vascular addressin cell adhesion molecule-1 (MAdCAM-1) or vascular cell adhesion molecule-1 (VCAM-1). However, the mechanism underlying the selective binding of different ligands by α4β7 remains obscure. In this study, we demonstrate that CCL25 and CXCL10 induce distinct active conformers of α4β7 with a high affinity for either MAdCAM-1 or VCAM-1...
May 22, 2018: Journal of Cell Biology
Vincent Amarh, Martin A White, David R F Leach
Chromosomal replication is the major source of spontaneous DNA double-strand breaks (DSBs) in living cells. Repair of these DSBs is essential for cell viability, and accuracy of repair is critical to avoid chromosomal rearrangements. Repair of replication-dependent DSBs occurs primarily by homologous recombination with a sister chromosome. However, this reaction has never been visualized at a defined chromosomal locus, so little is known about its spatial or temporal dynamics. Repair of a replication-independent DSB generated in Escherichia coli by a rare-cutting endonuclease leads to the formation of a bundle of RecA filaments...
May 22, 2018: Journal of Cell Biology
Yun-Fen Hung, Chiung-Ya Chen, Yi-Chun Shih, Hsin-Yu Liu, Chiao-Ming Huang, Yi-Ping Hsueh
Neuroinflammation is associated with diverse neurological disorders. Endosomal Toll-like receptors (TLRs) including TLR3, TLR7, and TLR8 cell-autonomously regulate neuronal differentiation. However, the mechanisms by which these three TLRs affect neuronal morphology are unclear. In this study, we compare these TLRs in mouse neurons. By combining in vitro neuronal cultures, in utero electroporation, and transcriptomic profiling, we show that TLR8, TLR7, and TLR3 promote dendritic pruning via MYD88 signaling...
May 18, 2018: Journal of Cell Biology
Marie Anne O'Donnell
Sanz-Moreno investigates how the cytoskeleton controls tumor biology.
May 18, 2018: Journal of Cell Biology
F Donelson Smith, John D Scott
The role of autophosphorylation of the type II regulatory subunit in activation of protein kinase A (PKA) has been a longstanding question. In this issue, Isensee et al. (2018. J. Cell Biol. use antibody tools that selectively recognize phosphorylated RII and the catalytic subunit active site to reexamine PKA holoenzyme activation mechanisms in neurons.
May 17, 2018: Journal of Cell Biology
Daniel Brayson, Chin Yee Ho, Catherine M Shanahan
In this issue, Wang et al. (2018. J. Cell Biol. show that disruption to different mechanical domains of muscle cells converge at the linker of nucleoskeleton to cytoskeleton complex to affect DNA endoreplication potentially via barrier to autointegration factor-mediated epigenetic mechanisms.
May 16, 2018: Journal of Cell Biology
Qiao-Chu Wang, Xi Wang, Tie-Shan Tang
STIM1 activates store-operated Ca2+ entry when Ca2+ in the endoplasmic reticulum (ER) is depleted. In this issue, Chang et al. (2018. J. Cell Biol. demonstrate that EB1 traps STIM1 at dynamic contacts between the ER and microtubule plus ends, delaying STIM1 translocation to ER-plasma membrane junctions and preventing Ca2+ overload.
May 15, 2018: Journal of Cell Biology
Motoko Takahashi, Toru Hirota
When and how sister chromatid resolution occurs after DNA replication is a fundamental question. Stanyte et al. (2018. J. Cell Biol. used CRISPR/Cas9 technology to label and track genomic loci in live cells throughout the cell cycle, shedding light on how replication is linked to mitotic sister chromatid organization.
May 15, 2018: Journal of Cell Biology
Juan Manuel Schvartzman, Craig B Thompson, Lydia W S Finley
Dynamic regulation of gene expression in response to changing local conditions is critical for the survival of all organisms. In metazoans, coherent regulation of gene expression programs underlies the development of functionally distinct cell lineages. The cooperation between transcription factors and the chromatin landscape enables precise control of gene expression in response to cell-intrinsic and cell-extrinsic signals. Many of the chemical modifications that decorate DNA and histones are adducts derived from intermediates of cellular metabolic pathways...
May 14, 2018: Journal of Cell Biology
Gary Yellen
The brain's energy demands are remarkable both in their intensity and in their moment-to-moment dynamic range. This perspective considers the evidence for Warburg-like aerobic glycolysis during the transient metabolic response of the brain to acute activation, and it particularly addresses the cellular mechanisms that underlie this metabolic response. The temporary uncoupling between glycolysis and oxidative phosphorylation led to the proposal of an astrocyte-to-neuron lactate shuttle whereby during stimulation, lactate produced by increased glycolysis in astrocytes is taken up by neurons as their primary energy source...
May 11, 2018: Journal of Cell Biology
Metin Aksu, Tino Pleiner, Samir Karaca, Christin Kappert, Heinz-Jürgen Dehne, Katharina Seibel, Henning Urlaub, Markus T Bohnsack, Dirk Görlich
Exportins bind cargo molecules in a RanGTP-dependent manner inside nuclei and transport them through nuclear pores to the cytoplasm. CRM1/Xpo1 is the best-characterized exportin because specific inhibitors such as leptomycin B allow straightforward cargo validations in vivo. The analysis of other exportins lagged far behind, foremost because no such inhibitors had been available for them. In this study, we explored the cargo spectrum of exportin 7/Xpo7 in depth and identified not only ∼200 potential export cargoes but also, surprisingly, ∼30 nuclear import substrates...
May 10, 2018: Journal of Cell Biology
Yutaka Ogawa, Naoko Imamoto
Appropriate cell growth conditions are limited to a narrow temperature range. Once the temperature is out of this range, cells respond to protect themselves, but temperature thresholds at which various intracellular responses occur, including nuclear transport systems, remain unclear. Using a newly developed precise temperature shift assay, we found that individual transport pathways have different sensitivities to a rise in temperature. Nuclear translocations of molecular chaperone HSP70s occur at a much lower temperature than the inhibition of Ran-dependent transport...
May 10, 2018: Journal of Cell Biology
Gabriel M Gihana, Tiffany R Musser, Oscar Thompson, Soni Lacefield
We investigated how Saccharomyces cerevisiae coordinate polarization, budding, and anaphase during a unique developmental program called return to growth (RTG) in which cells in meiosis return to mitosis upon nutrient shift. Cells reentering mitosis from prophase I deviate from the normal cell cycle by budding in G2 instead of G1. We found that cells do not maintain the bipolar budding pattern, a characteristic of diploid cells. Furthermore, strict temporal regulation of M-phase cyclin-dependent kinase (CDK; M-CDK) is important for polarity establishment and morphogenesis...
May 9, 2018: Journal of Cell Biology
Petra Zur Lage, Panagiota Stefanopoulou, Katarzyna Styczynska-Soczka, Niall Quinn, Girish Mali, Alex von Kriegsheim, Pleasantine Mill, Andrew P Jarman
The massive dynein motor complexes that drive ciliary and flagellar motility require cytoplasmic preassembly, a process requiring dedicated dynein assembly factors (DNAAFs). How DNAAFs interact with molecular chaperones to control dynein assembly is not clear. By analogy with the well-known multifunctional HSP90-associated cochaperone, R2TP, several DNAAFs have been suggested to perform novel R2TP-like functions. However, the involvement of R2TP itself (canonical R2TP) in dynein assembly remains unclear. Here we show that in Drosophila melanogaster , the R2TP-associated factor, Wdr92, is required exclusively for axonemal dynein assembly, likely in association with canonical R2TP...
May 9, 2018: Journal of Cell Biology
Carla A M Lopes, Marta Mesquita, Ana Isabel Cunha, Joana Cardoso, Sara Carapeta, Cátia Laranjeira, António E Pinto, José B Pereira-Leal, António Dias-Pereira, Mónica Bettencourt-Dias, Paula Chaves
Centrosome abnormalities are a typical hallmark of human cancers. However, the origin and dynamics of such abnormalities in human cancer are not known. In this study, we examined centrosomes in Barrett's esophagus tumorigenesis, a well-characterized multistep pathway of progression, from the premalignant condition to the metastatic disease. This human cancer model allows the study of sequential steps of progression within the same patient and has representative cell lines from all stages of disease. Remarkably, centrosome amplification was detected as early as the premalignant condition and was significantly expanded in dysplasia...
May 8, 2018: Journal of Cell Biology
Christoph Schiklenk, Boryana Petrova, Marc Kschonsak, Markus Hassler, Carlo Klein, Toby J Gibson, Christian H Haering
Although the formation of rod-shaped chromosomes is vital for the correct segregation of eukaryotic genomes during cell divisions, the molecular mechanisms that control the chromosome condensation process have remained largely unknown. Here, we identify the C2 H2 zinc-finger transcription factor Zas1 as a key regulator of mitotic condensation dynamics in a quantitative live-cell microscopy screen of the fission yeast Schizosaccharomyces pombe By binding to specific DNA target sequences in their promoter regions, Zas1 controls expression of the Cnd1 subunit of the condensin protein complex and several other target genes, whose combined misregulation in zas1 mutants results in defects in chromosome condensation and segregation...
May 7, 2018: Journal of Cell Biology
Michael T Kelliher, Yang Yue, Ashley Ng, Daichi Kamiyama, Bo Huang, Kristen J Verhey, Jill Wildonger
Neuronal polarity relies on the selective localization of cargo to axons or dendrites. The molecular motor kinesin-1 moves cargo into axons but is also active in dendrites. This raises the question of how kinesin-1 activity is regulated to maintain the compartment-specific localization of cargo. Our in vivo structure-function analysis of endogenous Drosophila melanogaster kinesin-1 reveals a novel role for autoinhibition in enabling the dendrite-specific localization of Golgi outposts. Mutations that disrupt kinesin-1 autoinhibition result in the axonal mislocalization of Golgi outposts...
May 4, 2018: Journal of Cell Biology
Kenta Shigetomi, Yumiko Ono, Tetsuichiro Inai, Junichi Ikenouchi
Tight junctions (TJs) are essential cell adhesion structures that act as a barrier to separate the internal milieu from the external environment in multicellular organisms. Although their major constituents have been identified, it is unknown how the formation of TJs is regulated. TJ formation depends on the preceding formation of adherens junctions (AJs) in epithelial cells; however, the underlying mechanism remains to be elucidated. In this study, loss of AJs in α-catenin-knockout (KO) EpH4 epithelial cells altered the lipid composition of the plasma membrane (PM) and led to endocytosis of claudins, a major component of TJs...
May 2, 2018: Journal of Cell Biology
WooRam Jung, Emma Sierecki, Michele Bastiani, Ailis O'Carroll, Kirill Alexandrov, James Rae, Wayne Johnston, Dominic J B Hunter, Charles Ferguson, Yann Gambin, Nicholas Ariotti, Robert G Parton
Caveolae have been linked to the regulation of signaling pathways in eukaryotic cells through direct interactions with caveolins. Here, we describe a cell-free system based on Leishmania tarentolae ( Lt ) extracts for the biogenesis of caveolae and show its use for single-molecule interaction studies. Insertion of expressed caveolin-1 (CAV1) into Lt membranes was analogous to that of caveolin in native membranes. Electron tomography showed that caveolins generate domains of precise size and curvature. Cell-free caveolae were used in quantitative assays to test the interaction of membrane-inserted caveolin with signaling proteins and to determine the stoichiometry of interactions...
May 1, 2018: Journal of Cell Biology
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