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Journal of Cell Biology

Luke M Rice
What does the end of a growing microtubule look like? In this issue, McIntosh et al. (2018. J. Cell Biol. use electron tomography to provide state-of-the-art three-dimensional images of microtubule ends in cells and in vitro, yielding an unexpected answer to this fundamental question.
July 13, 2018: Journal of Cell Biology
William Razzell, Maria E Bustillo, Jennifer A Zallen
The reorganization of cells in response to mechanical forces converts simple epithelial sheets into complex tissues of various shapes and dimensions. Epithelial integrity is maintained throughout tissue remodeling, but the mechanisms that regulate dynamic changes in cell adhesion under tension are not well understood. In Drosophila melanogaster , planar polarized actomyosin forces direct spatially organized cell rearrangements that elongate the body axis. We show that the LIM-domain protein Ajuba is recruited to adherens junctions in a tension-dependent fashion during axis elongation...
July 13, 2018: Journal of Cell Biology
Takamasa Inoue, Pengwei Zhang, Wei Zhang, Kylia Goodner-Bingham, Allison Dupzyk, Daniel DiMaio, Billy Tsai
Despite their importance as human pathogens, entry of human papillomaviruses (HPVs) into cells is poorly understood. The transmembrane protease γ-secretase executes a crucial function during the early stages of HPV infection, but the role of γ-secretase in infection and the identity of its critical substrate are unknown. Here we demonstrate that γ-secretase harbors a previously uncharacterized chaperone function, promoting low pH-dependent insertion of the HPV L2 capsid protein into endosomal membranes. Upon membrane insertion, L2 recruits the cytosolic retromer, which enables the L2 viral genome complex to enter the retrograde transport pathway and traffic to the Golgi en route for infection...
July 13, 2018: Journal of Cell Biology
Pauline Verlhac, Fulvio Reggiori
During micronucleophagy, the nucleolus is targeted by autophagic degradation, but although nucleolar proteins are recycled, ribosomal DNA is spared. Mostofa et al. (2018. J. Cell Biol. reveal that the separation of these two nucleolar components is mediated by the CLIP and cohibin complexes and is vital for cell survival during starvation.
July 13, 2018: Journal of Cell Biology
Sara Carvalhal, Alexandra Tavares, Mariana B Santos, Mihailo Mirkovic, Raquel A Oliveira
Sister chromatid cohesion mediated by cohesin is essential for mitotic fidelity. It counteracts spindle forces to prevent premature chromatid individualization and random genome segregation. However, it is unclear what effects a partial decline of cohesin may have on chromosome organization. In this study, we provide a quantitative analysis of cohesin decay by inducing acute removal of defined amounts of cohesin from metaphase-arrested chromosomes. We demonstrate that sister chromatid cohesion is very resistant to cohesin loss as chromatid disjunction is only observed when chromosomes lose >80% of bound cohesin...
July 12, 2018: Journal of Cell Biology
Marie Anne O'Donnell, Nicole Infarinato
Chipuk studies the interaction between mitochondrial dynamics and cell death in cancer.
July 10, 2018: Journal of Cell Biology
Chiara De Pascalis, Carlos Pérez-González, Shailaja Seetharaman, Batiste Boëda, Benoit Vianay, Mithila Burute, Cécile Leduc, Nicolas Borghi, Xavier Trepat, Sandrine Etienne-Manneville
Mesenchymal cell migration relies on the coordinated regulation of the actin and microtubule networks that participate in polarized cell protrusion, adhesion, and contraction. During collective migration, most of the traction forces are generated by the acto-myosin network linked to focal adhesions at the front of leader cells, which transmit these pulling forces to the followers. Here, using an in vitro wound healing assay to induce polarization and collective directed migration of primary astrocytes, we show that the intermediate filament (IF) network composed of vimentin, glial fibrillary acidic protein, and nestin contributes to directed collective movement by controlling the distribution of forces in the migrating cell monolayer...
July 6, 2018: Journal of Cell Biology
Marie-Hélène Verlhac
The large nuclei and tiny spindles of oocytes create a challenge for chromosome capture at M-phase entry. A contractile F-actin mesh in starfish oocytes delivers chromosomes to the spindle and Burdyniuk et al. (2018. J. Cell Biol. show that F-actin delays the capture of chromosomes until they are within reach of microtubules.
July 6, 2018: Journal of Cell Biology
Rocío G Sampayo, Andrés M Toscani, Matthew G Rubashkin, Kate Thi, Luciano A Masullo, Ianina L Violi, Jonathon N Lakins, Alfredo Cáceres, William C Hines, Federico Coluccio Leskow, Fernando D Stefani, Dante R Chialvo, Mina J Bissell, Valerie M Weaver, Marina Simian
Estrogen receptor α (ERα) is expressed in tissues as diverse as brains and mammary glands. In breast cancer, ERα is a key regulator of tumor progression. Therefore, understanding what activates ERα is critical for cancer treatment in particular and cell biology in general. Using biochemical approaches and superresolution microscopy, we show that estrogen drives membrane ERα into endosomes in breast cancer cells and that its fate is determined by the presence of fibronectin (FN) in the extracellular matrix; it is trafficked to lysosomes in the absence of FN and avoids the lysosomal compartment in its presence...
July 6, 2018: Journal of Cell Biology
Daphné Dambournet, Kem A Sochacki, Aaron T Cheng, Matthew Akamatsu, Justin W Taraska, Dirk Hockemeyer, David G Drubin
We developed a general approach for investigation of how cellular processes become adapted for specific cell types during differentiation. Previous studies reported substantial differences in the morphology and dynamics of clathrin-mediated endocytosis (CME) sites. However, associating specific CME properties with distinct differentiated cell types and determining how these properties are developmentally specified during differentiation have been elusive. Using genome-edited human embryonic stem cells, and isogenic fibroblasts and neuronal progenitor cells derived from them, we established by live-cell imaging and platinum replica transmission electron microscopy that CME site dynamics and ultrastructure on the plasma membrane are precisely reprogrammed during differentiation...
July 6, 2018: Journal of Cell Biology
Bong Hwan Sung, Alissa M Weaver
Directional cell motility toward a chemical gradient, chemotaxis, is critical during inflammation, embryogenesis, and cancer metastasis. In this issue, Kriebel et al. (2018. J. Cell Biol. demonstrate that the key cAMP chemoattractant for Dictyostelium discoideum amoebas is synthesized within and released from extracellular vesicles to promote chemotaxis.
July 5, 2018: Journal of Cell Biology
Katja Srpan, Ashley Ambrose, Alexandros Karampatzakis, Mezida Saeed, Adam N R Cartwright, Karolin Guldevall, Gabriela Dos Santos Cruz De Matos, Björn Önfelt, Daniel M Davis
Natural Killer (NK) cells can engage multiple virally infected or tumor cells sequentially and deliver perforin for cytolytic killing of these targets. Using microscopy to visualize degranulation from individual NK cells, we found that repeated activation via the Fc receptor CD16 decreased the amount of perforin secreted. However, perforin secretion was restored upon subsequent activation via a different activating receptor, NKG2D. Repeated stimulation via NKG2D also decreased perforin secretion, but this was not rescued by stimulation via CD16...
July 2, 2018: Journal of Cell Biology
Chen Yuan Kam, Adi D Dubash, Elisa Magistrati, Simona Polo, Karla J F Satchell, Farah Sheikh, Paul D Lampe, Kathleen J Green
Desmoplakin (DP) is an obligate component of desmosomes, intercellular adhesive junctions that maintain the integrity of the epidermis and myocardium. Mutations in DP can cause cardiac and cutaneous disease, including arrhythmogenic cardiomyopathy (ACM), an inherited disorder that frequently results in deadly arrhythmias. Conduction defects in ACM are linked to the remodeling and functional interference with Cx43-based gap junctions that electrically and chemically couple cells. How DP loss impairs gap junctions is poorly understood...
June 29, 2018: Journal of Cell Biology
Sebastian Wissel, Heike Harzer, François Bonnay, Thomas R Burkard, Ralph A Neumüller, Juergen A Knoblich
Drosophila melanogaster neural stem cells (neuroblasts [NBs]) divide asymmetrically by differentially segregating protein determinants into their daughter cells. Although the machinery for asymmetric protein segregation is well understood, the events that reprogram one of the two daughter cells toward terminal differentiation are less clear. In this study, we use time-resolved transcriptional profiling to identify the earliest transcriptional differences between the daughter cells on their way toward distinct fates...
June 29, 2018: Journal of Cell Biology
Md Golam Mostofa, Muhammad Arifur Rahman, Naoki Koike, Akter Mst Yeasmin, Nafisa Islam, Talukdar Muhammad Waliullah, Shun Hosoyamada, Mitsugu Shimobayashi, Takehiko Kobayashi, Michael N Hall, Takashi Ushimaru
Nutrient starvation or inactivation of target of rapamycin complex 1 (TORC1) in budding yeast induces nucleophagy, a selective autophagy process that preferentially degrades nucleolar components. DNA, including ribosomal DNA (rDNA), is not degraded by nucleophagy, even though rDNA is embedded in the nucleolus. Here, we show that TORC1 inactivation promotes relocalization of nucleolar proteins and rDNA to different sites. Nucleolar proteins move to sites proximal to the nuclear-vacuolar junction (NVJ), where micronucleophagy (or piecemeal microautophagy of the nucleus) occurs, whereas rDNA dissociates from nucleolar proteins and moves to sites distal to NVJs...
June 29, 2018: Journal of Cell Biology
Maria Dandoulaki, Eleni Petsalaki, David Sumpton, Sara Zanivan, George Zachos
In cytokinesis with chromatin bridges, cells delay abscission and retain actin patches at the intercellular canal to prevent chromosome breakage. In this study, we show that inhibition of Src, a protein-tyrosine kinase that regulates actin dynamics, or Chk1 kinase correlates with chromatin breakage and impaired formation of actin patches but not with abscission in the presence of chromatin bridges. Chk1 is required for optimal localization and complete activation of Src. Furthermore, Chk1 phosphorylates human Src at serine 51, and phosphorylated Src localizes to actin patches, the cell membrane, or the nucleus...
June 28, 2018: Journal of Cell Biology
Michael L Drummond, Mischa Li, Eric Tarapore, Tuyen T L Nguyen, Baina J Barouni, Shaun Cruz, Kevin C Tan, Anthony E Oro, Scott X Atwood
Primary cilia are polarized organelles that allow detection of extracellular signals such as Hedgehog (Hh). How the cytoskeleton supporting the cilium generates and maintains a structure that finely tunes cellular response remains unclear. Here, we find that regulation of actin polymerization controls primary cilia and Hh signaling. Disrupting actin polymerization, or knockdown of N-WASp/Arp3, increases ciliation frequency, axoneme length, and Hh signaling. Cdc42, a potent actin regulator, recruits both atypical protein pinase C iota/lambda (aPKC) and Missing-in-Metastasis (MIM) to the basal body to maintain actin polymerization and restrict axoneme length...
June 26, 2018: Journal of Cell Biology
Sungsu Lee, Han Yen Tan, Ivayla I Geneva, Aleksandr Kruglov, Peter D Calvert
Physical properties of primary cilia membranes in living cells were examined using two independent, high-spatiotemporal-resolution approaches: fast tracking of single quantum dot-labeled G protein-coupled receptors and a novel two-photon super-resolution fluorescence recovery after photobleaching of protein ensemble. Both approaches demonstrated the cilium membrane to be partitioned into corralled domains spanning 274 ± 20 nm, within which the receptors are transiently confined for 0.71 ± 0.09 s. The mean membrane diffusion coefficient within the corrals, Dm 1 = 2...
June 26, 2018: Journal of Cell Biology
Ihsan Zulkipli, Joanna Clark, Madeleine Hart, Roshan L Shrestha, Parveen Gul, David Dang, Tami Kasichiwin, Izabela Kujawiak, Nishanth Sastry, Viji M Draviam
The plane of cell division is defined by the final position of the mitotic spindle. The spindle is pulled and rotated to the correct position by cortical dynein. However, it is unclear how the spindle's rotational center is maintained and what the consequences of an equatorially off centered spindle are in human cells. We analyzed spindle movements in 100s of cells exposed to protein depletions or drug treatments and uncovered a novel role for MARK2 in maintaining the spindle at the cell's geometric center...
June 25, 2018: Journal of Cell Biology
Harald F Hofbauer, Michael Gecht, Sabine C Fischer, Anja Seybert, Achilleas S Frangakis, Ernst H K Stelzer, Roberto Covino, Gerhard Hummer, Robert Ernst
A key event in cellular physiology is the decision between membrane biogenesis and fat storage. Phosphatidic acid (PA) is an important intermediate at the branch point of these pathways and is continuously monitored by the transcriptional repressor Opi1 to orchestrate lipid metabolism. In this study, we report on the mechanism of membrane recognition by Opi1 and identify an amphipathic helix (AH) for selective binding of PA over phosphatidylserine (PS). The insertion of the AH into the membrane core renders Opi1 sensitive to the lipid acyl chain composition and provides a means to adjust membrane biogenesis...
June 25, 2018: Journal of Cell Biology
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