journal
https://read.qxmd.com/read/38448164/genome-scale-requirements-for-dynein-based-transport-revealed-by-a-high-content-arrayed-crispr-screen
#21
JOURNAL ARTICLE
Chun Hao Wong, Steven W Wingett, Chen Qian, Morag Rose Hunter, J Matthew Taliaferro, Douglas Ross-Thriepland, Simon L Bullock
The microtubule motor dynein plays a key role in cellular organization. However, little is known about how dynein's biosynthesis, assembly, and functional diversity are orchestrated. To address this issue, we have conducted an arrayed CRISPR loss-of-function screen in human cells using the distribution of dynein-tethered peroxisomes and early endosomes as readouts. From a genome-wide gRNA library, 195 validated hits were recovered and parsed into those impacting multiple dynein cargoes and those whose effects are restricted to a subset of cargoes...
May 6, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38448163/the-derlin-dfm1-couples-retrotranslocation-of-a-folded-protein-domain-to-its-proteasomal-degradation
#22
JOURNAL ARTICLE
Daniela G Vitali, Daniel Fonseca, Pedro Carvalho
Endoplasmic reticulum (ER) proteins are degraded by proteasomes in the cytosol through ER-associated degradation (ERAD). This process involves the retrotranslocation of substrates across the ER membrane, their ubiquitination, and membrane extraction by the Cdc48/Npl4/Ufd1 ATPase complex prior to delivery to proteasomes for degradation. How the presence of a folded luminal domain affects substrate retrotranslocation and this event is coordinated with subsequent ERAD steps remains unknown. Here, using a model substrate with a folded luminal domain, we showed that Cdc48 ATPase activity is sufficient to drive substrate retrotranslocation independently of ERAD membrane components...
May 6, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38448162/reciprocal-regulation-by-elm1-and-gin4-controls-septin-hourglass-assembly-and-remodeling
#23
JOURNAL ARTICLE
Joseph Marquardt, Xi Chen, Erfei Bi
The septin cytoskeleton is extensively regulated by posttranslational modifications, such as phosphorylation, to achieve the diversity of architectures including rings, hourglasses, and gauzes. While many of the phosphorylation events of septins have been extensively studied in the budding yeast Saccharomyces cerevisiae, the regulation of the kinases involved remains poorly understood. Here, we show that two septin-associated kinases, the LKB1/PAR-4-related kinase Elm1 and the Nim1/PAR-1-related kinase Gin4, regulate each other at two discrete points of the cell cycle...
May 6, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38407313/dynein-and-dynactin-move-long-range-but-are-delivered-separately-to-the-axon-tip
#24
JOURNAL ARTICLE
Alexander D Fellows, Michaela Bruntraeger, Thomas Burgold, Andrew R Bassett, Andrew P Carter
Axonal transport is essential for neuronal survival. This is driven by microtubule motors including dynein, which transports cargo from the axon tip back to the cell body. This function requires its cofactor dynactin and regulators LIS1 and NDEL1. Due to difficulties imaging dynein at a single-molecule level, it is unclear how this motor and its regulators coordinate transport along the length of the axon. Here, we use a neuron-inducible human stem cell line (NGN2-OPTi-OX) to endogenously tag dynein components and visualize them at a near-single molecule regime...
May 6, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38358349/alternative-mechanisms-of-notch-activation-by-partitioning-into-distinct-endosomal-domains
#25
JOURNAL ARTICLE
Hideyuki Shimizu, Samira Hosseini-Alghaderi, Simon A Woodcock, Martin Baron
Different membrane microdomain compositions provide unique environments that can regulate signaling receptor function. We identify microdomains on the endosome membrane of Drosophila endosomes, enriched in lipid-raft or clathrin/ESCRT-0, which are associated with Notch activation by distinct, ligand-independent mechanisms. Transfer of Notch between microdomains is regulated by Deltex and Suppressor of deltex ubiquitin ligases and is limited by a gate-keeper role for ESCRT complexes. Ubiquitination of Notch by Deltex recruits it to the clathrin/ESCRT-0 microdomain and enhances Notch activation by an ADAM10-independent/TRPML-dependent mechanism...
May 6, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38358348/vps13c-regulates-phospho-rab10-mediated-lysosomal-function-in-human-dopaminergic-neurons
#26
JOURNAL ARTICLE
Leonie F Schrӧder, Wesley Peng, Ge Gao, Yvette C Wong, Michael Schwake, Dimitri Krainc
Loss-of-function mutations in VPS13C are linked to early-onset Parkinson's disease (PD). While VPS13C has been previously studied in non-neuronal cells, the neuronal role of VPS13C in disease-relevant human dopaminergic neurons has not been elucidated. Using live-cell microscopy, we investigated the role of VPS13C in regulating lysosomal dynamics and function in human iPSC-derived dopaminergic neurons. Loss of VPS13C in dopaminergic neurons disrupts lysosomal morphology and dynamics with increased inter-lysosomal contacts, leading to impaired lysosomal motility and cellular distribution, as well as defective lysosomal hydrolytic activity and acidification...
May 6, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38334958/ras-g-domains-allosterically-contribute-to-the-recognition-of-lipid-headgroups-and-acyl-chains
#27
JOURNAL ARTICLE
Neha Arora, Huanwen Mu, Hong Liang, Wenting Zhao, Yong Zhou
Mutant RAS are major contributors to cancer and signal primarily from nanoclusters on the plasma membrane (PM). Their C-terminal membrane anchors are main features of membrane association. However, the same RAS isoform bound to different guanine nucleotides spatially segregate. Different RAS nanoclusters all enrich a phospholipid, phosphatidylserine (PS). These findings suggest more complex membrane interactions. Our electron microscopy-spatial analysis shows that wild-types, G12V mutants, and membrane anchors of isoforms HRAS, KRAS4A, and KRAS4B prefer distinct PS species...
May 6, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38512059/positioning-centrioles-and-centrosomes
#28
REVIEW
Matthew R Hannaford, Nasser M Rusan
Centrosomes are the primary microtubule organizer in eukaryotic cells. In addition to shaping the intracellular microtubule network and the mitotic spindle, centrosomes are responsible for positioning cilia and flagella. To fulfill these diverse functions, centrosomes must be properly located within cells, which requires that they undergo intracellular transport. Importantly, centrosome mispositioning has been linked to ciliopathies, cancer, and infertility. The mechanisms by which centrosomes migrate are diverse and context dependent...
April 1, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38506732/crosstalk-between-tgf-%C3%AE-and-egf-receptors-via-direct-phosphorylation
#29
JOURNAL ARTICLE
Aristidis Moustakas
Aristidis Moustakas discusses work from Ye-Guang Chen and colleagues (https://doi.org/10.1083/jcb.202307138) on a new mechanism by which TGF-β modulates HER2 signaling in mammary epithelia.
April 1, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38488722/correction-fission-independent-compartmentalization-of-mitochondria-during-budding-yeast-cell-division
#30
Saori R Yoshii, Yves Barral
No abstract text is available yet for this article.
April 1, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38477880/correction-cell-cycle-controls-long-range-calcium-signaling-in-the-regenerating-epidermis
#31
Jessica L Moore, Dhananjay Bhaskar, Feng Gao, Catherine Matte-Martone, Shuangshuang Du, Elizabeth Lathrop, Smirthy Ganesan, Lin Shao, Rachael Norris, Nil Campamà Sanz, Karl Annusver, Maria Kasper, Andy Cox, Caroline Hendry, Bastian Rieck, Smita Krishnaswamy, Valentina Greco
No abstract text is available yet for this article.
April 1, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38477879/broken-chromosomes-heading-into-mitosis-more-than-one-way-to-patch-a-flat-tire
#32
JOURNAL ARTICLE
C Luke Messer, Donald T Fox
A cell dealing with a broken chromosome in mitosis is like a driver dealing with a flat tire on the highway: damage repair must occur under non-ideal circumstances. Mitotic chromosome breaks encounter problems related to structures called micronuclei. These aberrant nuclei are linked to cell death, mutagenesis, and cancer. In the last few years, a flurry of studies illuminated two mechanisms that prevent mitotic problems related to micronuclei. One mechanism prevents micronuclei from forming during mitosis and involves DNA Polymerase Theta, a DNA repair regulator that patches up broken mitotic chromosomes...
April 1, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38477878/dpm1-modulates-desmosomal-adhesion-and-epidermal-differentiation-through-serpinb5
#33
JOURNAL ARTICLE
Maitreyi Rathod, Henriette Franz, Vivien Beyersdorfer, Marie-Therès Wanuske, Karen Leal Fischer, Pauline Hanns, Chiara Stüdle, Aude Zimmermann, Katarzyna Buczak, Camilla Schinner, Volker Spindler
Glycosylation is essential to facilitate cell-cell adhesion and differentiation. We determined the role of the dolichol phosphate mannosyltransferase (DPM) complex, a central regulator for glycosylation, for desmosomal adhesive function and epidermal differentiation. Deletion of the key molecule of the DPM complex, DPM1, in human keratinocytes resulted in weakened cell-cell adhesion, impaired localization of the desmosomal components desmoplakin and desmoglein-2, and led to cytoskeletal organization defects in human keratinocytes...
April 1, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38466168/an-inside-job-new-roles-for-apoe-at-the-lipid-droplet
#34
JOURNAL ARTICLE
Femke M Feringa, Rik van der Kant
The secreted ApoE protein is a major regulator of lipid transport between brain cells. In this issue, Windham et al. (https://doi.org/10.1083/jcb.202305003) uncover a novel intracellular role for ApoE at the lipid droplet surface, where it regulates lipid droplet size and composition.
April 1, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38466167/paxillin-phase-separation-promotes-focal-adhesion-assembly-and-integrin-signaling
#35
JOURNAL ARTICLE
Peigang Liang, Yuchen Wu, Shanyuan Zheng, Jiaqi Zhang, Shuo Yang, Jinfang Wang, Suibin Ma, Mengjun Zhang, Zhuang Gu, Qingfeng Liu, Wenxue Jiang, Qiong Xing, Bo Wang
Focal adhesions (FAs) are transmembrane protein assemblies mediating cell-matrix connection. Although protein liquid-liquid phase separation (LLPS) has been tied to the organization and dynamics of FAs, the underlying mechanisms remain unclear. Here, we experimentally tune the LLPS of PXN/Paxillin, an essential scaffold protein of FAs, by utilizing a light-inducible Cry2 system in different cell types. In addition to nucleating FA components, light-triggered PXN LLPS potently activates integrin signaling and subsequently accelerates cell spreading...
April 1, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38456969/two-ancient-membrane-pores-mediate-mitochondrial-nucleus-membrane-contact-sites
#36
JOURNAL ARTICLE
Jana Ovciarikova, Shikha Shikha, Alice Lacombe, Flavie Courjol, Rosalind McCrone, Wasim Hussain, Andrew Maclean, Leandro Lemgruber, Erica S Martins-Duarte, Mathieu Gissot, Lilach Sheiner
Coordination between nucleus and mitochondria is essential for cell survival, and thus numerous communication routes have been established between these two organelles over eukaryotic cell evolution. One route for organelle communication is via membrane contact sites, functional appositions formed by molecular tethers. We describe a novel nuclear-mitochondrial membrane contact site in the protozoan Toxoplasma gondii. We have identified specific contacts occurring at the nuclear pore and demonstrated an interaction between components of the nuclear pore and the mitochondrial protein translocon, highlighting them as molecular tethers...
April 1, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38456968/building-the-centrosome-plk-1-controls-multimerization-of-spd-5
#37
JOURNAL ARTICLE
Paul Conduit
Centrosome maturation relies on the assembly of an underlying molecular scaffold. In this issue of JCB, Rios et al. (https://doi.org/10.1083/jcb.202306142) use cross-linking mass spectrometry to reveal how PLK-1 phosphorylation promotes intermolecular SPD-5 self-association that is essential for scaffold formation.
April 1, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38456967/multivalent-coiled-coil-interactions-enable-full-scale-centrosome-assembly-and-strength
#38
JOURNAL ARTICLE
Manolo U Rios, Małgorzata A Bagnucka, Bryan D Ryder, Beatriz Ferreira Gomes, Nicole E Familiari, Kan Yaguchi, Matthew Amato, Weronika E Stachera, Łukasz A Joachimiak, Jeffrey B Woodruff
The outermost layer of centrosomes, called pericentriolar material (PCM), organizes microtubules for mitotic spindle assembly. The molecular interactions that enable PCM to assemble and resist external forces are poorly understood. Here, we use crosslinking mass spectrometry (XL-MS) to analyze PLK-1-potentiated multimerization of SPD-5, the main PCM scaffold protein in C. elegans. In the unassembled state, SPD-5 exhibits numerous intramolecular crosslinks that are eliminated after phosphorylation by PLK-1. Thus, phosphorylation induces a structural opening of SPD-5 that primes it for assembly...
April 1, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38429999/fatty-acid-binding-proteins-3-7-and-8-bind-cholesterol-and-facilitate-its-egress-from-lysosomes
#39
JOURNAL ARTICLE
Xian-Xiu Fang, Pengcheng Wei, Kai Zhao, Zhao-Chen Sheng, Bao-Liang Song, Lei Yin, Jie Luo
Cholesterol from low-density lipoprotein (LDL) can be transported to many organelle membranes by non-vesicular mechanisms involving sterol transfer proteins (STPs). Fatty acid-binding protein (FABP) 7 was identified in our previous study searching for new regulators of intracellular cholesterol trafficking. Whether FABP7 is a bona fide STP remains unknown. Here, we found that FABP7 deficiency resulted in the accumulation of LDL-derived cholesterol in lysosomes and reduced cholesterol levels on the plasma membrane...
April 1, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38429998/moonwalking-molecular-machines-unraveling-the-choreography-of-myosin-filament-assembly
#40
JOURNAL ARTICLE
Noah J Gurley, Mark Peifer
We have made tremendous progress in identifying the machines that shape the architecture of actin filaments. However, we know less about the mechanisms mediating myosin assembly at the supramolecular level. In this issue, Quintanilla et al. (https://doi.org/10.1083/jcb.202305023) provide important new insights into this process.
April 1, 2024: Journal of Cell Biology
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