Correction: ARFRP1 functions upstream of ARL1 and ARL5 to coordinate recruitment of tethering factors to the trans-Golgi network
Vol. 218, No. 11, November 4, 2019. 10.1083/jcb.201905097. The authors noticed an error in the scheme shown in Fig. 8 of their manuscript. Two arrows pointing from ARFRP1 to ARL1 through GEF were in the... (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - November 3, 2019 Category: Cytology Authors: Ishida, M., Bonifacino, J. S. Tags: Corrections Source Type: research
New factors for protein transport identified by a genome-wide CRISPRi screen in mammalian cells
In conclusion, our work identified and characterized new actors in the mechanisms of protein transport and secretion and opens stimulating perspectives for the use of our platform in physiological and pathological contexts. (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - November 3, 2019 Category: Cytology Authors: Bassaganyas, L., Popa, S. J., Horlbeck, M., Puri, C., Stewart, S. E., Campelo, F., Ashok, A., Butnaru, C. M., Brouwers, N., Heydari, K., Ripoche, J., Weissman, J., Rubinsztein, D. C., Schekman, R., Malhotra, V., Moreau, K., Villeneuve, J. Tags: Trafficking, Technology Tools Source Type: research
Cell ratcheting through the Sbf RabGEF directs force balancing and stepped apical constriction
During Drosophila melanogaster gastrulation, the invagination of the prospective mesoderm is driven by the pulsed constriction of apical surfaces. Here, we address the mechanisms by which the irreversibility of pulsed events is achieved while also permitting uniform epithelial behaviors to emerge. We use MSD-based analyses to identify contractile steps and find that when a trafficking pathway initiated by Sbf is disrupted, contractile steps become reversible. Sbf localizes to tubular, apical surfaces and associates with Rab35, where it promotes Rab GTP exchange. Interestingly, when Sbf/Rab35 function is compromised, the ap...
Source: Journal of Cell Biology - November 3, 2019 Category: Cytology Authors: Miao, H., Vanderleest, T. E., Jewett, C. E., Loerke, D., Blankenship, J. T. Tags: Cytoskeleton, Trafficking, Development Articles Source Type: research
Chemotherapy-induced senescent cancer cells engulf other cells to enhance their survival
In chemotherapy-treated breast cancer, wild-type p53 preferentially induces senescence over apoptosis, resulting in a persisting cell population constituting residual disease that drives relapse and poor patient survival via the senescence-associated secretory phenotype. Understanding the properties of tumor cells that allow survival after chemotherapy treatment is paramount. Using time-lapse and confocal microscopy to observe interactions of cells in treated tumors, we show here that chemotherapy-induced senescent cells frequently engulf both neighboring senescent or nonsenescent tumor cells at a remarkable frequency. Eng...
Source: Journal of Cell Biology - November 3, 2019 Category: Cytology Authors: Tonnessen-Murray, C. A., Frey, W. D., Rao, S. G., Shahbandi, A., Ungerleider, N. A., Olayiwola, J. O., Murray, L. B., Vinson, B. T., Chrisey, D. B., Lord, C. J., Jackson, J. G. Tags: Cell Cycle and Division, Cell Death and Autophagy, Cancer Articles Source Type: research
Arf6 regulates RhoB subcellular localization to control cancer cell invasion
The ADP-ribosylation factor 6 (Arf6) is a small GTPase that regulates endocytic recycling processes in concert with various effectors. Arf6 controls cytoskeletal organization and membrane trafficking; however, the detailed mechanisms of regulation remain poorly understood. Here, we report that Arf6 forms a complex with RhoB. The interaction between RhoB and Arf6 is mediated by the GCI (glycine, cysteine, and isoleucine) residues (188–190) of RhoB. Specific targeting of Arf6 to plasma membrane or mitochondrial membranes promotes recruitment and colocalization of RhoB to these membrane microdomains. Arf6 depletion prom...
Source: Journal of Cell Biology - November 3, 2019 Category: Cytology Authors: Zaoui, K., Rajadurai, C. V., Duhamel, S., Park, M. Tags: Cell Signaling, Migration, Motility, Biochemistry, Cancer Articles Source Type: research
Ancestral roles of the Fam20C family of secreted protein kinases revealed in C. elegans
Fam20C is a secreted protein kinase mutated in Raine syndrome, a human skeletal disorder. In vertebrates, bone and enamel proteins are major Fam20C substrates. However, Fam20 kinases are conserved in invertebrates lacking bone and enamel, suggesting other ancestral functions. We show that FAMK-1, the Caenorhabditis elegans Fam20C orthologue, contributes to fertility, embryogenesis, and development. These functions are not fulfilled when FAMK-1 is retained in the early secretory pathway. During embryogenesis, FAMK-1 maintains intercellular partitions and prevents multinucleation; notably, temperature elevation or lowering c...
Source: Journal of Cell Biology - November 3, 2019 Category: Cytology Authors: Gerson-Gurwitz, A., Worby, C. A., Lee, K.-Y., Khaliullin, R., Bouffard, J., Cheerambathur, D., Oegema, K., Cram, E. J., Dixon, J. E., Desai, A. Tags: Disease, Cell Signaling, Development Articles Source Type: research
A PINCH-1-Smurf1 signaling axis mediates mechano-regulation of BMPR2 and stem cell differentiation
We report here a signaling axis consisting of PINCH-1, SMAD specific E3 ubiquitin protein ligase 1 (Smurf1), and bone morphogenetic protein type 2 receptor (BMPR2) that links mechano-environment to MSC fate decision. PINCH-1 interacts with Smurf1, which inhibits the latter from interacting with BMPR2 and consequently suppresses BMPR2 degradation, resulting in augmented BMP signaling and MSC osteogenic differentiation (OD). Extracellular matrix (ECM) stiffening increases PINCH-1 level and consequently activates this signaling axis. Depletion of PINCH-1 blocks stiff ECM-induced BMP signaling and OD, whereas overexpression of...
Source: Journal of Cell Biology - November 3, 2019 Category: Cytology Authors: Guo, L., Wang, R., Zhang, K., Yuan, J., Wang, J., Wang, X., Ma, J., Wu, C. Tags: Stem Cells, Adhesion, Cell Signaling Articles Source Type: research
An intrinsic compartmentalization code for peripheral membrane proteins in photoreceptor neurons
In neurons, peripheral membrane proteins are enriched in subcellular compartments, where they play key roles, including transducing and transmitting information. However, little is known about the mechanisms underlying their compartmentalization. To explore the roles of hydrophobic and electrostatic interactions, we engineered probes consisting of lipidation motifs attached to fluorescent proteins by variously charged linkers and expressed them in Xenopus rod photoreceptors. Quantitative live cell imaging showed dramatic differences in distributions and dynamics of the probes, including presynapse and ciliary OS enrichment...
Source: Journal of Cell Biology - November 3, 2019 Category: Cytology Authors: Maza, N. A., Schiesser, W. E., Calvert, P. D. Tags: Cilia, Trafficking, Biophysics, Neuroscience Articles Source Type: research
Mating yeast cells use an intrinsic polarity site to assemble a pheromone-gradient tracking machine
The mating of budding yeast depends on chemotropism, a fundamental cellular process. The two yeast mating types secrete peptide pheromones that bind to GPCRs on cells of the opposite type. Cells find and contact a partner by determining the direction of the pheromone source and polarizing their growth toward it. Actin-directed secretion to the chemotropic growth site (CS) generates a mating projection. When pheromone-stimulated cells are unable to sense a gradient, they form mating projections where they would have budded in the next cell cycle, at a position called the default polarity site (DS). Numerous models have been...
Source: Journal of Cell Biology - November 3, 2019 Category: Cytology Authors: Wang, X., Tian, W., Banh, B. T., Statler, B.-M., Liang, J., Stone, D. E. Tags: Cell Signaling, Polarity, Systems and Computational Biology Articles Source Type: research
The PI(4)P phosphatase Sac2 controls insulin granule docking and release
Insulin granule biogenesis involves transport to, and stable docking at, the plasma membrane before priming and fusion. Defects in this pathway result in impaired insulin secretion and are a hallmark of type 2 diabetes. We now show that the phosphatidylinositol 4-phosphate phosphatase Sac2 localizes to insulin granules in a substrate-dependent manner and that loss of Sac2 results in impaired insulin secretion. Sac2 operates upstream of granule docking, since loss of Sac2 prevented granule tethering to the plasma membrane and resulted in both reduced granule density and number of exocytic events. Sac2 levels correlated posi...
Source: Journal of Cell Biology - November 3, 2019 Category: Cytology Authors: Nguyen, P. M., Gandasi, N. R., Xie, B., Sugahara, S., Xu, Y., Idevall-Hagren, O. Tags: Disease, Membrane and Lipid Biology, Trafficking, Physiology Articles Source Type: research
Insulin activates intracellular transport of lipid droplets to release triglycerides from the liver
Triglyceride-rich lipid droplets (LDs) are catabolized with high efficiency in hepatocytes to supply fatty acids for producing lipoprotein particles. Fasting causes a massive influx of adipose-derived fatty acids into the liver. The liver in the fasted state is therefore bloated with LDs but, remarkably, still continues to secrete triglycerides at a constant rate. Here we show that insulin signaling elevates phosphatidic acid (PA) dramatically on LDs in the fed state. PA then signals to recruit kinesin-1 motors, which transport LDs to the peripherally located smooth ER inside hepatocytes, where LDs are catabolized to produ...
Source: Journal of Cell Biology - November 3, 2019 Category: Cytology Authors: Kumar, M., Ojha, S., Rai, P., Joshi, A., Kamat, S. S., Mallik, R. Tags: Cytoskeleton, Trafficking, Metabolism Articles Source Type: research
ARFRP1 functions upstream of ARL1 and ARL5 to coordinate recruitment of distinct tethering factors to the trans-Golgi network
SNARE-mediated fusion of endosome-derived transport carriers with the trans-Golgi network (TGN) depends on the concerted action of two types of tethering factors: long coiled-coil tethers of the golgin family, and the heterotetrameric complex GARP. Whereas the golgins mediate long-distance capture of the carriers, GARP promotes assembly of the SNAREs. It remains to be determined, however, how the functions of these tethering factors are coordinated. Herein we report that the ARF-like (ARL) GTPase ARFRP1 functions upstream of two other ARL GTPases, ARL1 and ARL5, which in turn recruit golgins and GARP, respectively, to the ...
Source: Journal of Cell Biology - November 3, 2019 Category: Cytology Authors: Ishida, M., Bonifacino, J. S. Tags: Organelles, Trafficking Articles Source Type: research
Seipin negatively regulates sphingolipid production at the ER-LD contact site
Seipin is known for its critical role in controlling lipid droplet (LD) assembly at the LD-forming subdomain of the endoplasmic reticulum (ER). Here, we identified a new function of seipin as a negative regulator for sphingolipid production. We show that yeast cells lacking seipin displayed altered sensitivity to sphingolipid inhibitors, accumulated sphingoid precursors and intermediates, and increased serine palmitoyltransferase (SPT) and fatty acid (FA) elongase activities. Seipin associated with SPT and FA elongase, and the interaction was reduced by inhibitors for sphingolipid synthesis in a concentration-dependent man...
Source: Journal of Cell Biology - November 3, 2019 Category: Cytology Authors: Su, W.-C., Lin, Y.-H., Pagac, M., Wang, C.-W. Tags: Membrane and Lipid Biology, Metabolism Articles Source Type: research
Loss of myosin Vb promotes apical bulk endocytosis in neonatal enterocytes
In patients with inactivating mutations in myosin Vb (Myo5B), enterocytes show large inclusions lined by microvilli. The origin of inclusions in small-intestinal enterocytes in microvillus inclusion disease is currently unclear. We postulated that inclusions in Myo5b KO mouse enterocytes form through invagination of the apical brush border membrane. 70-kD FITC-dextran added apically to Myo5b KO intestinal explants accumulated in intracellular inclusions. Live imaging of Myo5b KO–derived enteroids confirmed the formation of inclusions from the apical membrane. Treatment of intestinal explants and enteroids with Dyngo ...
Source: Journal of Cell Biology - November 3, 2019 Category: Cytology Authors: Engevik, A. C., Kaji, I., Postema, M. M., Faust, J. J., Meyer, A. R., Williams, J. A., Fitz, G. N., Tyska, M. J., Wilson, J. M., Goldenring, J. R. Tags: Trafficking, Development Articles Source Type: research
LIS1 regulates cargo-adapter-mediated activation of dynein by overcoming its autoinhibition in vivo
Deficiency of the LIS1 protein causes lissencephaly, a brain developmental disorder. Although LIS1 binds the microtubule motor cytoplasmic dynein and has been linked to dynein function in many experimental systems, its mechanism of action remains unclear. Here, we revealed its function in cargo-adapter–mediated dynein activation in the model organism Aspergillus nidulans. Specifically, we found that overexpressed cargo adapter HookA (Hook in A. nidulans) missing its cargo-binding domain (C-HookA) causes dynein and its regulator dynactin to relocate from the microtubule plus ends to the minus ends, and this relocation...
Source: Journal of Cell Biology - November 3, 2019 Category: Cytology Authors: Qiu, R., Zhang, J., Xiang, X. Tags: Cytoskeleton, Genetics Articles Source Type: research
