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Journal of Cell Biology

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https://www.readbyqxmd.com/read/28432080/npm1-directs-piddosome-dependent-caspase-2-activation-in-the-nucleolus
#1
Kiyohiro Ando, Melissa J Parsons, Richa B Shah, Chloé I Charendoff, Sheré L Paris, Peter H Liu, Sara R Fassio, Brittany A Rohrman, Ruth Thompson, Andrew Oberst, Samuel Sidi, Lisa Bouchier-Hayes
The PIDDosome (PIDD-RAIDD-caspase-2 complex) is considered to be the primary signaling platform for caspase-2 activation in response to genotoxic stress. Yet studies of PIDD-deficient mice show that caspase-2 activation can proceed in the absence of PIDD. Here we show that DNA damage induces the assembly of at least two distinct activation platforms for caspase-2: a cytoplasmic platform that is RAIDD dependent but PIDD independent, and a nucleolar platform that requires both PIDD and RAIDD. Furthermore, the nucleolar phosphoprotein nucleophosmin (NPM1) acts as a scaffold for PIDD and is essential for PIDDosome assembly in the nucleolus after DNA damage...
April 21, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28432079/regulation-of-microtubule-associated-motors-drives-intermediate-filament-network-polarization
#2
Cécile Leduc, Sandrine Etienne-Manneville
Intermediate filaments (IFs) are key players in the control of cell morphology and structure as well as in active processes such as cell polarization, migration, and mechanoresponses. However, the regulatory mechanisms controlling IF dynamics and organization in motile cells are still poorly understood. In this study, we investigate the mechanisms leading to the polarized rearrangement of the IF network along the polarity axis. Using photobleaching and photoconversion experiments in glial cells expressing vimentin, glial fibrillary acidic protein, and nestin, we show that the distribution of cytoplasmic IFs results from a continuous turnover based on the cooperation of an actin-dependent retrograde flow and anterograde and retrograde microtubule-dependent transports...
April 21, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28428367/copii-coated-membranes-function-as-transport-carriers-of-intracellular-procollagen-i
#3
Amita Gorur, Lin Yuan, Samuel J Kenny, Satoshi Baba, Ke Xu, Randy Schekman
The coat protein complex II (COPII) is essential for the transport of large cargo, such as 300-nm procollagen I (PC1) molecules, from the endoplasmic reticulum (ER) to the Golgi. Previous work has shown that the CUL3-KLHL12 complex increases the size of COPII vesicles at ER exit sites to more than 300 nm in diameter and accelerates the secretion of PC1. However, the role of large COPII vesicles as PC1 transport carriers was not unambiguously demonstrated. In this study, using stochastic optical reconstruction microscopy, correlated light electron microscopy, and live-cell imaging, we demonstrate the existence of mobile COPII-coated vesicles that completely encapsulate the cargo PC1 and are physically separated from ER...
April 20, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28424218/gop-1-promotes-apoptotic-cell-degradation-by-activating-the-small-gtpase-rab2-in-c-elegans
#4
Jianhua Yin, Yaling Huang, Pengfei Guo, Siqi Hu, Sawako Yoshina, Nan Xuan, Qiwen Gan, Shohei Mitani, Chonglin Yang, Xiaochen Wang
Apoptotic cells generated by programmed cell death are engulfed by phagocytes and enclosed within plasma membrane-derived phagosomes. Maturation of phagosomes involves a series of membrane-remodeling events that are governed by the sequential actions of Rab GTPases and lead to formation of phagolysosomes, where cell corpses are degraded. Here we identified gop-1 as a novel regulator of apoptotic cell clearance in Caenorhabditis elegans Loss of gop-1 affects phagosome maturation through the RAB-5-positive stage, causing defects in phagosome acidification and phagolysosome formation, phenotypes identical to and unaffected by loss of unc-108, the C...
April 19, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28416479/suppression-of-integrin-%C3%AE-3%C3%AE-1-by-%C3%AE-9%C3%AE-1-in-the-epidermis-controls-the-paracrine-resolution-of-wound-angiogenesis
#5
Whitney M Longmate, Scott P Lyons, Sridar V Chittur, Kevin M Pumiglia, Livingston Van De Water, C Michael DiPersio
Development of wound therapies is hindered by poor understanding of combinatorial integrin function in the epidermis. In this study, we generated mice with epidermis-specific deletion of α3β1, α9β1, or both integrins as well as keratinocyte lines expressing these integrin combinations. Consistent with proangiogenic roles for α3β1, α3-null keratinocytes showed reduced paracrine stimulation of endothelial cell migration and survival, and wounds of epidermis-specific α3 knockout mice displayed impaired angiogenesis...
April 17, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28416478/stardust-the-janus-faced-partner-of-crumbs
#6
Shradha Das, Elisabeth Knust
The Drosophila melanogaster scaffolding protein Stardust (Sdt) stabilizes the transmembrane protein Crumbs, a conserved regulator of apical-basal epithelial polarity. In this issue, Perez-Mockus et al. (2017. J. Cell Biol https://doi.org/10.1083/jcb.201611196) report that a subset of Sdt isoforms are targeted by the ubiquitin ligase Neuralized, thus fine tuning the endocytosis and activity of this apical determinant.
April 17, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28416477/actin-filament-assembly-by-bacterial-factors-vopl-f-which-end-is-up
#7
Christina L Vizcarra, Margot E Quinlan
Competing models have been proposed for actin filament nucleation by the bacterial proteins VopL/F. In this issue, Burke et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201608104) use direct observation to demonstrate that VopL/F bind the barbed and pointed ends of actin filaments but only nucleate new filaments from the pointed end.
April 17, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28416476/the-signal-hypothesis-matures-with-age
#8
Ben Short
Secretory proteins are targeted for secretion by sequences in their mature domains, as well as by N-terminal signal peptides.
April 17, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28411190/the-evolutionary-origins-of-antagonistic-neurotrophin-signaling
#9
Austin B Keeler, Christopher D Deppmann
A competitive balance between constructive and destructive developmental cues governs both the form and function of the vertebrate nervous system. In this issue, Foldi et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201607098) explore the evolutionary origins of these cues and report that in Drosophila melanogaster pro- and mature neurotrophins are capable of inducing death and survival pathways, respectively, by binding Toll receptor family members, which then recruit distinct sets of effector proteins...
April 14, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28411189/centrioles-initiate-cilia-assembly-but-are-dispensable-for-maturation-and-maintenance-in-c-elegans
#10
Daniel Serwas, Tiffany Y Su, Max Roessler, Shaohe Wang, Alexander Dammermann
Cilia are cellular projections that assemble on centriole-derived basal bodies. While cilia assembly is absolutely dependent on centrioles, it is not known to what extent they contribute to downstream events. The nematode C. elegans provides a unique opportunity to address this question, as centrioles do not persist at the base of mature cilia. Using fluorescence microscopy and electron tomography, we find that centrioles degenerate early during ciliogenesis. The transition zone and axoneme are not completely formed at this time, indicating that cilia maturation does not depend on intact centrioles...
April 14, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28408404/smurf1-inhibits-integrin-activation-by-controlling-kindlin-2-ubiquitination-and-degradation
#11
Xiaofan Wei, Xiang Wang, Jun Zhan, Yuhan Chen, Weigang Fang, Lingqiang Zhang, Hongquan Zhang
Integrin activation is an indispensable step for various integrin-mediated biological functions. Kindlin-2 is known to coactivate integrins with Talin; however, molecules that restrict integrin activation are elusive. Here, we demonstrate that the E3 ubiquitin ligase Smurf1 controls the amount of Kindlin-2 protein in cells and hinders integrin activation. Smurf1 interacts with and promotes Kindlin-2 ubiquitination and degradation. Smurf1 selectively mediates degradation of Kindlin-2 but not Talin, leading to inhibition of αIIbβ3 integrin activation in Chinese hamster ovary cells and β1 integrin activation in fibroblasts...
April 13, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28408403/antonina-roll-mecak-decoding-the-secrets-of-tubulin-complexity
#12
Timothy K Spencer
Antonina Roll-Mecak studies how tubulin variability modulates the specificity, complexity, and function of the microtubule network.
April 13, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28404644/preprotein-mature-domains-contain-translocase-targeting-signals-that-are-essential-for-secretion
#13
Katerina E Chatzi, Marios Frantzeskos Sardis, Alexandra Tsirigotaki, Marina Koukaki, Nikolina Šoštarić, Albert Konijnenberg, Frank Sobott, Charalampos G Kalodimos, Spyridoula Karamanou, Anastassios Economou
Secretory proteins are only temporary cytoplasmic residents. They are typically synthesized as preproteins, carrying signal peptides N-terminally fused to their mature domains. In bacteria secretion largely occurs posttranslationally through the membrane-embedded SecA-SecYEG translocase. Upon crossing the plasma membrane, signal peptides are cleaved off and mature domains reach their destinations and fold. Targeting to the translocase is mediated by signal peptides. The role of mature domains in targeting and secretion is unclear...
April 12, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28404643/the-beach-containing-protein-wdr81-coordinates-p62-and-lc3c-to-promote-aggrephagy
#14
Xuezhao Liu, Yang Li, Xin Wang, Ruxiao Xing, Kai Liu, Qiwen Gan, Changyong Tang, Zhiyang Gao, Youli Jian, Shouqing Luo, Weixiang Guo, Chonglin Yang
Autophagy-dependent clearance of ubiquitinated and aggregated proteins is critical to protein quality control, but the underlying mechanisms are not well understood. Here, we report the essential role of the BEACH (beige and Chediak-Higashi) and WD40 repeat-containing protein WDR81 in eliminating ubiquitinated proteins through autophagy. WDR81 associates with ubiquitin (Ub)-positive protein foci, and its loss causes accumulation of Ub proteins and the autophagy cargo receptor p62. WDR81 interacts with p62, facilitating recognition of Ub proteins by p62...
April 12, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28404642/squeezing-out-in-a-tug-of-war-the-role-of-myosin-in-neural-stem-cell-delamination
#15
Clara Sidor, Katja Röper
Neural stem cells or neuroblasts in the Drosophila melanogaster embryo delaminate as single cells from the embryonic epidermis to give rise to the nervous system. Using this accessible system to examine the molecular mechanisms of cell ingression at a high temporal and spatial resolution, in this issue, Simões et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201608038) reveal that myosin-driven anisotropic junction loss and apical constriction are the main drivers of this process.
April 12, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28400444/shaping-proteostasis-at-the-cellular-tissue-and-organismal-level
#16
REVIEW
Ambre J Sala, Laura C Bott, Richard I Morimoto
The proteostasis network (PN) regulates protein synthesis, folding, transport, and degradation to maintain proteome integrity and limit the accumulation of protein aggregates, a hallmark of aging and degenerative diseases. In multicellular organisms, the PN is regulated at the cellular, tissue, and systemic level to ensure organismal health and longevity. Here we review these three layers of PN regulation and examine how they collectively maintain cellular homeostasis, achieve cell type-specific proteomes, and coordinate proteostasis across tissues...
April 11, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28400443/plastin-increases-cortical-connectivity-to-facilitate-robust-polarization-and-timely-cytokinesis
#17
Wei Yung Ding, Hui Ting Ong, Yusuke Hara, Jantana Wongsantichon, Yusuke Toyama, Robert C Robinson, François Nédélec, Ronen Zaidel-Bar
The cell cortex is essential to maintain animal cell shape, and contractile forces generated within it by nonmuscle myosin II (NMY-2) drive cellular morphogenetic processes such as cytokinesis. The role of actin cross-linking proteins in cortical dynamics is still incompletely understood. Here, we show that the evolutionarily conserved actin bundling/cross-linking protein plastin is instrumental for the generation of potent cortical actomyosin contractility in the Caenorhabditis elegans zygote. PLST-1 was enriched in contractile structures and was required for effective coalescence of NMY-2 filaments into large contractile foci and for long-range coordinated contractility in the cortex...
April 11, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28400442/peripherin-diverts-ciliary-ectosome-release-to-photoreceptor-disc-morphogenesis
#18
Robert S Molday, Andrew F X Goldberg
Formation of membrane discs in photoreceptor cells requires evagination of its ciliary plasma membrane by an unknown molecular mechanism. Salinas et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201608081) show that peripherin (also known as peripherin-2 or peripherin-2/rds) diverts membrane traffic to photoreceptor disc formation by inhibiting ectosome release from the cilium.
April 11, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28400441/neuralized-regulates-crumbs-endocytosis-and-epithelium-morphogenesis-via-specific-stardust-isoforms
#19
Gantas Perez-Mockus, Vanessa Roca, Khalil Mazouni, François Schweisguth
Crumbs (Crb) is a conserved determinant of apical membrane identity that regulates epithelial morphogenesis in many developmental contexts. In this study, we identify the Crb complex protein Stardust (Sdt) as a target of the E3 ubiquitin ligase Neuralized (Neur) in Drosophila melanogaster Neur interacts with and down-regulates specific Sdt isoforms containing a Neur binding motif (NBM). Using a CRISPR (clustered regularly interspaced short palindromic repeats)-induced deletion of the NBM-encoding exon, we found that Sdt is a key Neur target and that Neur acts via Sdt to down-regulate Crb...
April 10, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28389476/defects-in-er-endosome-contacts-impact-lysosome-function-in-hereditary-spastic-paraplegia
#20
Rachel Allison, James R Edgar, Guy Pearson, Tania Rizo, Timothy Newton, Sven Günther, Fiamma Berner, Jennifer Hague, James W Connell, Jürgen Winkler, Jennifer Lippincott-Schwartz, Christian Beetz, Beate Winner, Evan Reid
Contacts between endosomes and the endoplasmic reticulum (ER) promote endosomal tubule fission, but the mechanisms involved and consequences of tubule fission failure are incompletely understood. We found that interaction between the microtubule-severing enzyme spastin and the ESCRT protein IST1 at ER-endosome contacts drives endosomal tubule fission. Failure of fission caused defective sorting of mannose 6-phosphate receptor, with consequently disrupted lysosomal enzyme trafficking and abnormal lysosomal morphology, including in mouse primary neurons and human stem cell-derived neurons...
April 7, 2017: Journal of Cell Biology
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