Correction: A Ca2+-stimulated exosome release pathway in cancer cells is regulated by Munc13-4
Vol. 217, No. 8, August 6, 2018. 10.1083/jcb.201710132. The top blot shown in Fig. S1 A was mistakenly inverted prior to publication. The corrected Fig. S1 is shown below. The text and figure... (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - March 31, 2019 Category: Cytology Authors: Messenger, S. W., Woo, S. S., Sun, Z., Martin, T. F. J. Tags: Corrections Source Type: research

Correction: The binding of NCAM to FGFR1 induces a specific cellular response mediated by receptor trafficking
Vol. 187, No. 7, December 28, 2009. 10.1083/jcb.200903030. Following publication, the authors realized that Fig. 6 A inadvertently contained an incorrect image for the 30-min treatment with FGL in the presence of SU6656 (in the... (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - March 31, 2019 Category: Cytology Authors: Francavilla, C., Cattaneo, P., Berezin, V., Bock, E., Ami, D., de Marco, A., Christofori, G., Cavallaro, U. Tags: Corrections Source Type: research

Novel tool to quantify cell wall porosity relates wall structure to cell growth and drug uptake
Even though cell walls have essential functions for bacteria, fungi, and plants, tools to investigate their dynamic structure in living cells have been missing. Here, it is shown that changes in the intensity of the plasma membrane dye FM4-64 in response to extracellular quenchers depend on the nano-scale porosity of cell walls. The correlation of quenching efficiency and cell wall porosity is supported by tests on various cell types, application of differently sized quenchers, and comparison of results with confocal, electron, and atomic force microscopy images. The quenching assay was used to investigate how changes in c...
Source: Journal of Cell Biology - March 31, 2019 Category: Cytology Authors: Liu, X., Li, J., Zhao, H., Liu, B., Günther-Pomorski, T., Chen, S., Liesche, J. Tags: Membrane and Lipid Biology, Microbiology, Plant Biology Tools Source Type: research

The Wave complex controls epidermal morphogenesis and proliferation by suppressing Wnt-Sox9 signaling
Development of the skin epidermis requires tight spatiotemporal control over the activity of several signaling pathways; however, the mechanisms that orchestrate these events remain poorly understood. Here, we identify a key role for the Wave complex proteins ABI1 and Wave2 in regulating signals that control epidermal shape and growth. In utero RNAi-mediated silencing of Abi1 or Wasf2 induced cellular hyperproliferation and defects in architecture of the interfollicular epidermis (IFE) and delayed hair follicle growth. Unexpectedly, SOX9, a hair follicle growth regulator, was aberrantly expressed throughout the IFE of the ...
Source: Journal of Cell Biology - March 31, 2019 Category: Cytology Authors: Cohen, J., Raviv, S., Adir, O., Padmanabhan, K., Soffer, A., Luxenburg, C. Tags: Cytoskeleton, Cell Signaling, Development Articles Source Type: research

YAP and TAZ limit cytoskeletal and focal adhesion maturation to enable persistent cell motility
Cell migration initiates by traction generation through reciprocal actomyosin tension and focal adhesion reinforcement, but continued motility requires adaptive cytoskeletal remodeling and adhesion release. Here, we asked whether de novo gene expression contributes to this cytoskeletal feedback. We found that global inhibition of transcription or translation does not impair initial cell polarization or migration initiation, but causes eventual migratory arrest through excessive cytoskeletal tension and over-maturation of focal adhesions, tethering cells to their matrix. The transcriptional coactivators YAP and TAZ mediate ...
Source: Journal of Cell Biology - March 31, 2019 Category: Cytology Authors: Mason, D. E., Collins, J. M., Dawahare, J. H., Nguyen, T. D., Lin, Y., Voytik-Harbin, S. L., Zorlutuna, P., Yoder, M. C., Boerckel, J. D. Tags: Cytoskeleton, Migration, Motility, Biophysics Articles Source Type: research

Coenzyme Q biosynthetic proteins assemble in a substrate-dependent manner into domains at ER-mitochondria contacts
Coenzyme Q (CoQ) lipids are ancient electron carriers that, in eukaryotes, function in the mitochondrial respiratory chain. In mitochondria, CoQ lipids are built by an inner membrane–associated, multicomponent, biosynthetic pathway via successive steps of isoprenyl tail polymerization, 4-hydroxybenzoate head-to-tail attachment, and head modification, resulting in the production of CoQ. In yeast, we discovered that head-modifying CoQ pathway components selectively colocalize to multiple resolvable domains in vivo, representing supramolecular assemblies. In cells engineered with conditional ON or OFF CoQ pathways, doma...
Source: Journal of Cell Biology - March 31, 2019 Category: Cytology Authors: Subramanian, K., Jochem, A., Le Vasseur, M., Lewis, S., Paulson, B. R., Reddy, T. R., Russell, J. D., Coon, J. J., Pagliarini, D. J., Nunnari, J. Tags: Membrane and Lipid Biology, Metabolism Articles Source Type: research

Cerebellar ataxia disease-associated Snx14 promotes lipid droplet growth at ER-droplet contacts
Lipid droplets (LDs) are nutrient reservoirs used by cells to maintain homeostasis. Nascent droplets form on the endoplasmic reticulum (ER) and grow following an influx of exogenous fatty acids (FAs). The budding of LDs requires extensive ER–LD crosstalk, but how this is regulated remains poorly understood. Here, we show that sorting nexin protein Snx14, an ER-resident protein associated with the cerebellar ataxia SCAR20, localizes to ER–LD contacts following FA treatment, where it promotes LD maturation. Using proximity-based APEX technology and topological dissection, we show that Snx14 accumulates specifical...
Source: Journal of Cell Biology - March 31, 2019 Category: Cytology Authors: Datta, S., Liu, Y., Hariri, H., Bowerman, J., Henne, W. M. Tags: Organelles, Membrane and Lipid Biology, Biochemistry Articles Source Type: research

Mdm1 maintains endoplasmic reticulum homeostasis by spatially regulating lipid droplet biogenesis
Lipid droplets (LDs) serve as cytoplasmic reservoirs for energy-rich fatty acids (FAs) stored in the form of triacylglycerides (TAGs). During nutrient stress, yeast LDs cluster adjacent to the vacuole/lysosome, but how this LD accumulation is coordinated remains poorly understood. The ER protein Mdm1 is a molecular tether that plays a role in clustering LDs during nutrient depletion, but its mechanism of function remains unknown. Here, we show that Mdm1 associates with LDs through its hydrophobic N-terminal region, which is sufficient to demarcate sites for LD budding. Mdm1 binds FAs via its Phox-associated domain and coen...
Source: Journal of Cell Biology - March 31, 2019 Category: Cytology Authors: Hariri, H., Speer, N., Bowerman, J., Rogers, S., Fu, G., Reetz, E., Datta, S., Feathers, J. R., Ugrankar, R., Nicastro, D., Henne, W. M. Tags: Organelles, Membrane and Lipid Biology, Genetics Articles Source Type: research

MAP7 family proteins regulate kinesin-1 recruitment and activation
Kinesin-1 is responsible for microtubule-based transport of numerous cellular cargoes. Here, we explored the regulation of kinesin-1 by MAP7 proteins. We found that all four mammalian MAP7 family members bind to kinesin-1. In HeLa cells, MAP7, MAP7D1, and MAP7D3 act redundantly to enable kinesin-1–dependent transport and microtubule recruitment of the truncated kinesin-1 KIF5B-560, which contains the stalk but not the cargo-binding and autoregulatory regions. In vitro, purified MAP7 and MAP7D3 increase microtubule landing rate and processivity of kinesin-1 through transient association with the motor. MAP7 proteins p...
Source: Journal of Cell Biology - March 31, 2019 Category: Cytology Authors: Hooikaas, P. J., Martin, M., Mühlethaler, T., Kuijntjes, G.-J., Peeters, C. A. E., Katrukha, E. A., Ferrari, L., Stucchi, R., Verhagen, D. G. F., van Riel, W. E., Grigoriev, I., Altelaar, A. F. M., Hoogenraad, C. C., Rüdiger, S. G. D., Ste Tags: Cytoskeleton, Biochemistry Articles Source Type: research

Protein stability of p53 targets determines their temporal expression dynamics in response to p53 pulsing
This study delineates the mechanisms by which p53 dynamics play a crucial role in orchestrating the timing of events in the DNA damage response network. (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - March 31, 2019 Category: Cytology Authors: Hanson, R. L., Porter, J. R., Batchelor, E. Tags: Cell Signaling, Systems and Computational Biology Articles Source Type: research

Cyclin B3 promotes anaphase I onset in oocyte meiosis
Meiosis poses unique challenges because two rounds of chromosome segregation must be executed without intervening DNA replication. Mammalian cells express numerous temporally regulated cyclins, but how these proteins collaborate to control meiosis remains poorly understood. Here, we show that female mice genetically ablated for cyclin B3 are viable—indicating that the protein is dispensable for mitotic divisions—but are sterile. Mutant oocytes appear normal until metaphase I but then display a highly penetrant failure to transition to anaphase I. They arrest with hallmarks of defective anaphase-promoting comple...
Source: Journal of Cell Biology - March 31, 2019 Category: Cytology Authors: Karasu, M. E., Bouftas, N., Keeney, S., Wassmann, K. Tags: Cell Cycle and Division, Development, Genetics Articles Source Type: research

PLK1 plays dual roles in centralspindlin regulation during cytokinesis
Cytokinesis begins upon anaphase onset. An early step involves local activation of the small GTPase RhoA, which triggers assembly of an actomyosin-based contractile ring at the equatorial cortex. Here, we delineated the contributions of PLK1 and Aurora B to RhoA activation and cytokinesis initiation in human cells. Knock-down of PRC1, which disrupts the spindle midzone, revealed the existence of two pathways that can initiate cleavage furrow ingression. One pathway depends on a well-organized spindle midzone and PLK1, while the other depends on Aurora B activity and centralspindlin at the equatorial cortex and can operate ...
Source: Journal of Cell Biology - March 31, 2019 Category: Cytology Authors: Adriaans, I. E., Basant, A., Ponsioen, B., Glotzer, M., Lens, S. M. A. Tags: Cell Cycle and Division, Cell Signaling Articles Source Type: research

Quantitative phosphoproteomics reveals mitotic function of the ATR activator ETAA1
The ATR kinase controls cell cycle transitions and the DNA damage response. ATR activity is regulated through two ATR-activating proteins, ETAA1 and TOPBP1. To examine how each activator contributes to ATR signaling, we used quantitative mass spectrometry to identify changes in protein phosphorylation in ETAA1- or TOPBP1-deficient cells. We identified 724, 285, and 118 phosphosites to be regulated by TOPBP1, ETAA1, or both ATR activators, respectively. Gene ontology analysis of TOPBP1- and ETAA1-dependent phosphoproteins revealed TOPBP1 to be a primary ATR activator for replication stress, while ETAA1 regulates mitotic ATR...
Source: Journal of Cell Biology - March 31, 2019 Category: Cytology Authors: Bass, T. E., Cortez, D. Tags: Cell Cycle and Division, DNA Biology, Biochemistry Articles Source Type: research

Kinesin-binding protein ensures accurate chromosome segregation by buffering KIF18A and KIF15
Mitotic kinesins must be regulated to ensure a precise balance of spindle forces and accurate segregation of chromosomes into daughter cells. Here, we demonstrate that kinesin-binding protein (KBP) reduces the activity of KIF18A and KIF15 during metaphase. Overexpression of KBP disrupts the movement and alignment of mitotic chromosomes and decreases spindle length, a combination of phenotypes observed in cells deficient for KIF18A and KIF15, respectively. We show through gliding filament and microtubule co-pelleting assays that KBP directly inhibits KIF18A and KIF15 motor activity by preventing microtubule binding. Consist...
Source: Journal of Cell Biology - March 31, 2019 Category: Cytology Authors: Malaby, H. L. H., Dumas, M. E., Ohi, R., Stumpff, J. Tags: Cell Cycle and Division, Biochemistry, Biophysics Articles Source Type: research

Eph signaling controls mitotic spindle orientation and cell proliferation in neuroepithelial cells
Mitotic spindle orientation must be tightly regulated during development and adult tissue homeostasis. It determines cell-fate specification and tissue architecture during asymmetric and symmetric cell division, respectively. Here, we uncover a novel role for Ephrin–Eph intercellular signaling in controlling mitotic spindle alignment in Drosophila optic lobe neuroepithelial cells through aPKC activity–dependent myosin II regulation. We show that conserved core components of the mitotic spindle orientation machinery, including Discs Large1, Mud/NuMA, and Canoe/Afadin, mislocalize in dividing Eph mutant neuroepit...
Source: Journal of Cell Biology - March 31, 2019 Category: Cytology Authors: Franco, M., Carmena, A. Tags: Cell Cycle and Division, Cell Signaling, Development Articles Source Type: research