Deubiquitinating enzyme USP30 maintains basal peroxisome abundance by regulating pexophagy
In this study, we characterize a role of the deubiquitinating enzyme USP30 in peroxisome maintenance. Peroxisomes are highly dynamic, changing in abundance in response to metabolic stress. In our recent study identifying the role of USP30 in mitophagy, we observed USP30 to be localized to punctate structures resembling peroxisomes. We report here that USP30, best known as a mitophagy regulator, is also necessary for regulating pexophagy, the selective autophagic degradation of peroxisomes. We find that overexpressing USP30 prevents pexophagy during amino acid starvation, and its depletion results in pexophagy induction und...
Source: Journal of Cell Biology - March 3, 2019 Category: Cytology Authors: Riccio, V., Demers, N., Hua, R., Vissa, M., Cheng, D. T., Strilchuk, A. W., Wang, Y., McQuibban, G. A., Kim, P. K. Tags: Organelles, Cell Death and Autophagy, Biochemistry Reports Source Type: research
The activity of Sac1 across ER-TGN contact sites requires the four-phosphate-adaptor-protein-1
Phosphatidylinositol-4-phosphate (PI4P), a phosphoinositide with key roles in the Golgi complex, is made by Golgi-associated phosphatidylinositol-4 kinases and consumed by the 4-phosphatase Sac1 that, instead, is an ER membrane protein. Here, we show that the contact sites between the ER and the TGN (ERTGoCS) provide a spatial setting suitable for Sac1 to dephosphorylate PI4P at the TGN. The ERTGoCS, though necessary, are not sufficient for the phosphatase activity of Sac1 on TGN PI4P, since this needs the phosphatidyl-four-phosphate-adaptor-protein-1 (FAPP1). FAPP1 localizes at ERTGoCS, interacts with Sac1, and promotes i...
Source: Journal of Cell Biology - March 3, 2019 Category: Cytology Authors: Venditti, R., Masone, M. C., Rega, L. R., Di Tullio, G., Santoro, M., Polishchuk, E., Serrano, I. C., Olkkonen, V. M., Harada, A., Medina, D. L., La Montagna, R., De Matteis, M. A. Tags: Organelles, Metabolism Reports Source Type: research
Asymmetric division through a reduction of microtubule centering forces
Asymmetric divisions are essential for the generation of cell fate and size diversity. They implicate cortical domains where minus end–directed motors, such as dynein, are activated to pull on microtubules to decenter asters attached to centrosomes, nuclei, or spindles. In asymmetrically dividing cells, aster decentration typically follows a centering phase, suggesting a time-dependent regulation in the competition between microtubule centering and decentering forces. Using symmetrically dividing sea urchin zygotes, we generated cortical domains of magnetic particles that spontaneously cluster endogenous dynein activ...
Source: Journal of Cell Biology - March 3, 2019 Category: Cytology Authors: Salle, J., Xie, J., Ershov, D., Lacassin, M., Dmitrieff, S., Minc, N. Tags: Cytoskeleton, Cell Cycle and Division, Development Reports Source Type: research
Autophagosome maturation: An epic journey from the ER to lysosomes
Macroautophagy involves the sequestration of cytoplasmic contents in a double-membrane autophagosome and their delivery to lysosomes for degradation. In multicellular organisms, nascent autophagosomes fuse with vesicles originating from endolysosomal compartments before forming degradative autolysosomes, a process known as autophagosome maturation. ATG8 family members, tethering factors, Rab GTPases, and SNARE proteins act coordinately to mediate fusion of autophagosomes with endolysosomal vesicles. The machinery mediating autophagosome maturation is under spatiotemporal control and provides regulatory nodes to integrate n...
Source: Journal of Cell Biology - March 3, 2019 Category: Cytology Authors: Zhao, Y. G., Zhang, H. Tags: Cell Death and Autophagy Review Source Type: research
Scribble: A master scaffold in polarity, adhesion, synaptogenesis, and proliferation
Key events ranging from cell polarity to proliferation regulation to neuronal signaling rely on the assembly of multiprotein adhesion or signaling complexes at particular subcellular sites. Multidomain scaffolding proteins nucleate assembly and direct localization of these complexes, and the protein Scribble and its relatives in the LAP protein family provide a paradigm for this. Scribble was originally identified because of its role in apical–basal polarity and epithelial integrity in Drosophila melanogaster. It is now clear that Scribble acts to assemble and position diverse multiprotein complexes in processes rang...
Source: Journal of Cell Biology - March 3, 2019 Category: Cytology Authors: Bonello, T. T., Peifer, M. Tags: Adhesion, Development Review Source Type: research
TAPPing into PIPs: A new reporter reveals the origin of plasma membrane PI(3,4)P2
The membrane lipid phosphatidylinositol-3,4-bisphosphate (PI(3,4)P2) is an important signaling effector, controlling both anabolic pathways and membrane trafficking. In this issue, Goulden et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201809026) report a new PI(3,4)P2 probe and show that plasma membrane PI(3,4)P2 is a product of PI(3,4,5)P3 dephosphorylation. (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - March 3, 2019 Category: Cytology Authors: Yudushkin, I. Tags: Spotlight Source Type: research
Sense and sensibility: ATM oxygen stress signaling manages brain cell energetics
The ataxia-telangiectasia mutated (ATM) gene regulates DNA damage repair, oxidative stress, and mitochondrial processes. In this issue, Chow et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201806197) connects ATM’s oxidative stress response functions to the sensing of metabolic ATP energetics distinctively important in high energy–demanding Purkinje brain cells, which could explain the most distinct A-T patient feature, cerebellar ataxia. (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - March 3, 2019 Category: Cytology Authors: Schlacher, K. Tags: Spotlight Source Type: research
Staying in touch: Taking a closer look at ER-Golgi contact sites
ER–Golgi contact sites regulate lipid homeostasis and trafficking across the trans-Golgi network. However, their molecular nature is elusive. In this issue, Venditti et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201812020 and https://doi.org/10.1083/jcb.201812021) shine new light on the molecular determinants coupling lipid exchange and cargo exit with maintenance of ER–Golgi contacts. (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - March 3, 2019 Category: Cytology Authors: Sassano, M. L., Agostinis, P. Tags: Spotlight Source Type: research
Resistance is futile: Centering forces yield for asymmetric cell division
Asymmetric cell division relies on microtubule-based forces to asymmetrically position the mitotic apparatus. In this issue, Sallé et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201807102) use magnetic tweezers to induce asymmetric division in sea urchin zygotes, demonstrating that asymmetry could arise from a time-dependent weakening of centering forces. (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - March 3, 2019 Category: Cytology Authors: Alper, J., Zanic, M. Tags: Spotlight Source Type: research
Mahak Sharma: Weaving through traffic
Sharma investigates vesicular trafficking to lysosomes and how pathogens hijack the endolysosomal system during infection. (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - March 3, 2019 Category: Cytology Authors: Infarinato, N. Tags: People & amp;amp; Ideas Source Type: research
Correction: Microtubule reorientation in the blue spotlight: Cutting and CLASPing at dynamic hot spots
Vol. 218, No. 1, January 7, 2019. 10.1083/jcb.201812063. Following publication, the JCB staff noted errors in the in-text citations and order of papers in the reference list that were introduced during production of the article. The authors... (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - February 4, 2019 Category: Cytology Authors: Benoit, B., Poüs, C. Tags: Corrections Source Type: research
Correction: Going the distance: Neocentromeres make long-range contacts with heterochromatin
Vol. 218, No. 1, January 7, 2019. 10.1083/jcb.201811172. Following publication, the JCB staff noted errors in the in-text citations and order of papers in the reference list that were introduced during production of the article. The authors... (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - February 4, 2019 Category: Cytology Authors: McNulty, S. M., Sullivan, B. A. Tags: Corrections Source Type: research
Cocaine-induced release of CXCL10 from pericytes regulates monocyte transmigration into the CNS
Cocaine is known to facilitate the transmigration of inflammatory leukocytes into the brain, an important mechanism underlying neuroinflammation. Pericytes are well-recognized as important constituents of the blood–brain barrier (BBB), playing a key role in maintaining barrier integrity. In the present study, we demonstrate for the first time that exposure of human brain vascular pericytes to cocaine results in enhanced secretion of CXCL10, leading, in turn, to increased monocyte transmigration across the BBB both in vitro and in vivo. This process involved translocation of -1 receptor (-1R) and interaction of -1R wi...
Source: Journal of Cell Biology - February 4, 2019 Category: Cytology Authors: Niu, F., Liao, K., Hu, G., Sil, S., Callen, S., Guo, M.-l., Yang, L., Buch, S. Tags: Cell Signaling, Migration, Motility, Immunology Articles Source Type: research
Single event visualization of unconventional secretion of FGF2
FGF2 is exported from cells by an unconventional secretory mechanism. Here, we directly visualized individual FGF2 membrane translocation events at the plasma membrane using live cell TIRF microscopy. This process was dependent on both PI(4,5)P2–mediated recruitment of FGF2 at the inner leaflet and heparan sulfates capturing FGF2 at the outer plasma membrane leaflet. By simultaneous imaging of both FGF2 membrane recruitment and the appearance of FGF2 at the cell surface, we revealed the kinetics of FGF2 membrane translocation in living cells with an average duration of ~200 ms. Furthermore, we directly demonstrated F...
Source: Journal of Cell Biology - February 4, 2019 Category: Cytology Authors: Dimou, E., Cosentino, K., Platonova, E., Ros, U., Sadeghi, M., Kashyap, P., Katsinelos, T., Wegehingel, S., Noe, F., Garcia-Saez, A. J., Ewers, H., Nickel, W. Tags: Membrane and Lipid Biology, Trafficking, Biophysics Articles Source Type: research
BAR scaffolds drive membrane fission by crowding disordered domains
Cellular membranes are continuously remodeled. The crescent-shaped bin-amphiphysin-rvs (BAR) domains remodel membranes in multiple cellular pathways. Based on studies of isolated BAR domains in vitro, the current paradigm is that BAR domain–containing proteins polymerize into cylindrical scaffolds that stabilize lipid tubules. But in nature, proteins that contain BAR domains often also contain large intrinsically disordered regions. Using in vitro and live cell assays, here we show that full-length BAR domain–containing proteins, rather than stabilizing membrane tubules, are instead surprisingly potent drivers ...
Source: Journal of Cell Biology - February 4, 2019 Category: Cytology Authors: Snead, W. T., Zeno, W. F., Kago, G., Perkins, R. W., Richter, J. B., Zhao, C., Lafer, E. M., Stachowiak, J. C. Tags: Membrane and Lipid Biology, Trafficking, Biophysics Articles Source Type: research
