journal
https://read.qxmd.com/read/38536036/the-gtpase-activating-protein-gyp7-regulates-rab7-ypt7-activity-on-late-endosomes
#1
JOURNAL ARTICLE
Nadia Füllbrunn, Raffaele Nicastro, Muriel Mari, Janice Griffith, Eric Herrmann, René Rasche, Ann-Christin Borchers, Kathrin Auffarth, Daniel Kümmel, Fulvio Reggiori, Claudio De Virgilio, Lars Langemeyer, Christian Ungermann
Organelles of the endomembrane system contain Rab GTPases as identity markers. Their localization is determined by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs). It remains largely unclear how these regulators are specifically targeted to organelles and how their activity is regulated. Here, we focus on the GAP Gyp7, which acts on the Rab7-like Ypt7 protein in yeast, and surprisingly observe the protein exclusively in puncta proximal to the vacuole. Mistargeting of Gyp7 to the vacuole strongly affects vacuole morphology, suggesting that endosomal localization is needed for function...
June 3, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38536035/ddx6-modulates-p-body-and-stress-granule-assembly-composition-and-docking
#2
JOURNAL ARTICLE
Nina Ripin, Luisa Macedo de Vasconcelos, Daniella A Ugay, Roy Parker
Stress granules and P-bodies are ribonucleoprotein (RNP) granules that accumulate during the stress response due to the condensation of untranslating mRNPs. Stress granules form in part by intermolecular RNA-RNA interactions and can be limited by components of the RNA chaperone network, which inhibits RNA-driven aggregation. Herein, we demonstrate that the DEAD-box helicase DDX6, a P-body component, can also limit the formation of stress granules, independent of the formation of P-bodies. In an ATPase, RNA-binding dependent manner, DDX6 limits the partitioning of itself and other RNPs into stress granules...
June 3, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38530252/phosphatidylserine-regulates-plasma-membrane-repair-through-tetraspanin-enriched-macrodomains
#3
JOURNAL ARTICLE
Yang E Li, Dougall M Norris, Fanqian N Xiao, Elvis Pandzic, Renee M Whan, Sandra Fok, Ming Zhou, Guangwei Du, Yang Liu, Ximing Du, Hongyuan Yang
The integrity of the plasma membrane is critical to cell function and survival. Cells have developed multiple mechanisms to repair damaged plasma membranes. A key process during plasma membrane repair is to limit the size of the damage, which is facilitated by the presence of tetraspanin-enriched rings surrounding damage sites. Here, we identify phosphatidylserine-enriched rings surrounding damaged sites of the plasma membrane, resembling tetraspanin-enriched rings. Importantly, the formation of both the phosphatidylserine- and tetraspanin-enriched rings requires phosphatidylserine and its transfer proteins ORP5 and ORP9...
June 3, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38526325/m6am-methyltransferase-pcif1-negatively-regulates-ciliation-by-inhibiting-bicd2-expression
#4
JOURNAL ARTICLE
Shanshan Xie, Wenjun Kuang, Mengzhe Guo, Feng Yang, Hao Jin, Xiying Chen, Li Yi, Chunxiao Huo, Zhangqi Xu, Aifu Lin, Wei Liu, Jianhua Mao, Qiang Shu, Tianhua Zhou
N6, 2'-O-dimethyladenosine (m6Am) is a widespread RNA modification catalyzed by the methyltransferase PCIF1 (phosphorylated CTD interacting factor 1). Despite its prevalence, the biological functions of m6Am in RNA remain largely elusive. Here, we report a critical role of PCIF1-dependent m6Am RNA modification in ciliogenesis in RPE-1 cells. Our findings demonstrate that PCIF1 acts as a negative regulator of ciliation through its m6Am methyltransferase activity. A quantitative proteomic analysis identifies BICD2 as a downstream target of PCIF1, with PCIF1 depletion resulting in a significant increase in BICD2 levels...
June 3, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38512027/rab3-phosphorylation-by-pathogenic-lrrk2-impairs-trafficking-of-synaptic-vesicle-precursors
#5
JOURNAL ARTICLE
Dan Dou, Jayne Aiken, Erika L F Holzbaur
Gain-of-function mutations in the LRRK2 gene cause Parkinson's disease (PD), characterized by debilitating motor and non-motor symptoms. Increased phosphorylation of a subset of RAB GTPases by LRRK2 is implicated in PD pathogenesis. We find that increased phosphorylation of RAB3A, a cardinal synaptic vesicle precursor (SVP) protein, disrupts anterograde axonal transport of SVPs in iPSC-derived human neurons (iNeurons) expressing hyperactive LRRK2-p.R1441H. Knockout of the opposing protein phosphatase 1H (PPM1H) in iNeurons phenocopies this effect...
June 3, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38506714/lift-out-cryo-fibsem-and-cryo-et-reveal-the-ultrastructural-landscape-of-extracellular-matrix
#6
JOURNAL ARTICLE
Bettina Zens, Florian Fäßler, Jesse M Hansen, Robert Hauschild, Julia Datler, Victor-Valentin Hodirnau, Vanessa Zheden, Jonna Alanko, Michael Sixt, Florian K M Schur
The extracellular matrix (ECM) serves as a scaffold for cells and plays an essential role in regulating numerous cellular processes, including cell migration and proliferation. Due to limitations in specimen preparation for conventional room-temperature electron microscopy, we lack structural knowledge on how ECM components are secreted, remodeled, and interact with surrounding cells. We have developed a 3D-ECM platform compatible with sample thinning by cryo-focused ion beam milling, the lift-out extraction procedure, and cryo-electron tomography...
June 3, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38497788/fascin-induced-bundling-protects-actin-filaments-from-disassembly-by-cofilin
#7
JOURNAL ARTICLE
Jahnavi Chikireddy, Léana Lengagne, Rémi Le Borgne, Catherine Durieu, Hugo Wioland, Guillaume Romet-Lemonne, Antoine Jégou
Actin filament turnover plays a central role in shaping actin networks, yet the feedback mechanism between network architecture and filament assembly dynamics remains unclear. The activity of ADF/cofilin, the main protein family responsible for filament disassembly, has been mainly studied at the single filament level. This study unveils that fascin, by crosslinking filaments into bundles, strongly slows down filament disassembly by cofilin. We show that this is due to a markedly slower initiation of the first cofilin clusters, which occurs up to 100-fold slower on large bundles compared with single filaments...
June 3, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38488622/ww-domains-form-a-folded-type-of-nuclear-localization-signal-to-guide-yap1-nuclear-import
#8
JOURNAL ARTICLE
Yilin Yang, Mengxiao Wu, Yu Pan, Yue Hua, Xinyu He, Xinyang Li, Jiyong Wang, Xiaoqing Gan
The nuclear translocation of YAP1 is significantly implicated in the proliferation, stemness, and metastasis of cancer cells. Although the molecular basis underlying YAP1 subcellular distribution has been extensively explored, it remains to be elucidated how the nuclear localization signal guides YAP1 to pass through the nuclear pore complex. Here, we define a globular type of nuclear localization signal composed of folded WW domains, named as WW-NLS. It directs YAP1 nuclear import through the heterodimeric nuclear transport receptors KPNA-KPNB1, bypassing the canonical nuclear localization signal that has been well documented in KPNA/KPNB1-mediated nuclear import...
June 3, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38478018/snare-chaperone-sly1-directly-mediates-close-range-vesicle-tethering
#9
JOURNAL ARTICLE
Mengtong Duan, Rachael L Plemel, Tomoka Takenaka, Ariel Lin, Beatriz Marie Delgado, Una Nattermann, Daniel P Nickerson, Joji Mima, Elizabeth A Miller, Alexey J Merz
The essential Golgi protein Sly1 is a member of the Sec1/mammalian Unc-18 (SM) family of SNARE chaperones. Sly1 was originally identified through remarkable gain-of-function alleles that bypass requirements for diverse vesicle tethering factors. Employing genetic analyses and chemically defined reconstitutions of ER-Golgi fusion, we discovered that a loop conserved among Sly1 family members is not only autoinhibitory but also acts as a positive effector. An amphipathic lipid packing sensor (ALPS)-like helix within the loop directly binds high-curvature membranes...
June 3, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38478017/sm-protein-sly1-and-a-snare-habc-domain-promote-membrane-fusion-through-multiple-mechanisms
#10
JOURNAL ARTICLE
Mengtong Duan, Guanbin Gao, Ariel Lin, Emma J Mackey, David K Banfield, Alexey J Merz
SM proteins including Sly1 are essential cofactors of SNARE-mediated membrane fusion. Using SNARE and Sly1 mutants and chemically defined in vitro assays, we separate and assess proposed mechanisms through which Sly1 augments fusion: (i) opening the closed conformation of the Qa-SNARE Sed5; (ii) close-range tethering of vesicles to target organelles, mediated by the Sly1-specific regulatory loop; and (iii) nucleation of productive trans-SNARE complexes. We show that all three mechanisms are important and operate in parallel, and that close-range tethering promotes trans-complex assembly when cis-SNARE assembly is a competing process...
June 3, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38477830/n-cadherin-dynamically-regulates-pediatric-glioma-cell-migration-in-complex-environments
#11
JOURNAL ARTICLE
Dayoung Kim, James M Olson, Jonathan A Cooper
Pediatric high-grade gliomas are highly invasive and essentially incurable. Glioma cells migrate between neurons and glia, along axon tracts, and through extracellular matrix surrounding blood vessels and underlying the pia. Mechanisms that allow adaptation to such complex environments are poorly understood. N-cadherin is highly expressed in pediatric gliomas and associated with shorter survival. We found that intercellular homotypic N-cadherin interactions differentially regulate glioma migration according to the microenvironment, stimulating migration on cultured neurons or astrocytes but inhibiting invasion into reconstituted or astrocyte-deposited extracellular matrix...
June 3, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38530280/oma1-protease-eliminates-arrested-protein-import-intermediates-upon-mitochondrial-depolarization
#12
JOURNAL ARTICLE
Magda Krakowczyk, Anna M Lenkiewicz, Tomasz Sitarz, Dominika Malinska, Mayra Borrero, Ben Hur Marins Mussulini, Vanessa Linke, Andrzej A Szczepankiewicz, Joanna M Biazik, Agata Wydrych, Hanna Nieznanska, Remigiusz A Serwa, Agnieszka Chacinska, Piotr Bragoszewski
Most mitochondrial proteins originate from the cytosol and require transport into the organelle. Such precursor proteins must be unfolded to pass through translocation channels in mitochondrial membranes. Misfolding of transported proteins can result in their arrest and translocation failure. Arrested proteins block further import, disturbing mitochondrial functions and cellular proteostasis. Cellular responses to translocation failure have been defined in yeast. We developed the cell line-based translocase clogging model to discover molecular mechanisms that resolve failed import events in humans...
May 6, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38517380/tight-junction-membrane-proteins-regulate-the-mechanical-resistance-of-the-apical-junctional-complex
#13
JOURNAL ARTICLE
Thanh Phuong Nguyen, Tetsuhisa Otani, Motosuke Tsutsumi, Noriyuki Kinoshita, Sachiko Fujiwara, Tomomi Nemoto, Toshihiko Fujimori, Mikio Furuse
Epithelia must be able to resist mechanical force to preserve tissue integrity. While intercellular junctions are known to be important for the mechanical resistance of epithelia, the roles of tight junctions (TJs) remain to be established. We previously demonstrated that epithelial cells devoid of the TJ membrane proteins claudins and JAM-A completely lack TJs and exhibit focal breakages of their apical junctions. Here, we demonstrate that apical junctions fracture when claudin/JAM-A-deficient cells undergo spontaneous cell stretching...
May 6, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38517379/the-emerging-roles-of-non-canonical-ubiquitination-in-proteostasis-and-beyond
#14
JOURNAL ARTICLE
Yoshino Akizuki, Stephanie Kaypee, Fumiaki Ohtake, Fumiyo Ikeda
Ubiquitin regulates various cellular functions by posttranslationally modifying substrates with diverse ubiquitin codes. Recent discoveries of new ubiquitin chain topologies, types of bonds, and non-protein substrates have substantially expanded the complexity of the ubiquitin code. Here, we describe the ubiquitin system covering the basic principles and recent discoveries related to mechanisms, technologies, and biological importance.
May 6, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38506728/crosstalk-within-and-beyond-the-polycomb-repressive-system
#15
JOURNAL ARTICLE
Tianyi Hideyuki Shi, Hiroki Sugishita, Yukiko Gotoh
The development of multicellular organisms depends on spatiotemporally controlled differentiation of numerous cell types and their maintenance. To generate such diversity based on the invariant genetic information stored in DNA, epigenetic mechanisms, which are heritable changes in gene function that do not involve alterations to the underlying DNA sequence, are required to establish and maintain unique gene expression programs. Polycomb repressive complexes represent a paradigm of epigenetic regulation of developmentally regulated genes, and the roles of these complexes as well as the epigenetic marks they deposit, namely H3K27me3 and H2AK119ub, have been extensively studied...
May 6, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38497895/the-phospholipids-cardiolipin-and-phosphatidylethanolamine-differentially-regulate-mdc-biogenesis
#16
JOURNAL ARTICLE
Tianyao Xiao, Alyssa M English, Zachary N Wilson, J Alan Maschek, James E Cox, Adam L Hughes
Cells utilize multiple mechanisms to maintain mitochondrial homeostasis. We recently characterized a pathway that remodels mitochondria in response to metabolic alterations and protein overload stress. This remodeling occurs via the formation of large membranous structures from the mitochondrial outer membrane called mitochondrial-derived compartments (MDCs), which are eventually released from mitochondria and degraded. Here, we conducted a microscopy-based screen in budding yeast to identify factors that regulate MDC formation...
May 6, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38477922/laura-feltri-of-schwann-cells-matrix-and-family
#17
JOURNAL ARTICLE
Stefano C Previtali, Carla Taveggia
No abstract text is available yet for this article.
May 6, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38470363/polarized-localization-of-kinesin-1-and-ric-7-drives-axonal-mitochondria-anterograde-transport
#18
JOURNAL ARTICLE
Youjun Wu, Chen Ding, Behrang Sharif, Alexis Weinreb, Grace Swaim, Hongyan Hao, Shaul Yogev, Shigeki Watanabe, Marc Hammarlund
Mitochondria transport is crucial for axonal mitochondria distribution and is mediated by kinesin-1-based anterograde and dynein-based retrograde motor complexes. While Miro and Milton/TRAK were identified as key adaptors between mitochondria and kinesin-1, recent studies suggest the presence of additional mechanisms. In C. elegans, ric-7 is the only single gene described so far, other than kinesin-1, that is absolutely required for axonal mitochondria localization. Using CRISPR engineering in C. elegans, we find that Miro is important but is not essential for anterograde traffic, whereas it is required for retrograde traffic...
May 6, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38470362/p24-tango1-interactions-ensure-er-golgi-interface-stability-and-efficient-transport
#19
JOURNAL ARTICLE
Ke Yang, Zhi Feng, José Carlos Pastor-Pareja
The eukaryotic p24 family, consisting of α-, β-, γ- and δ-p24 subfamilies, has long been known to be involved in regulating secretion. Despite increasing interest in these proteins, fundamental questions remain about their role. Here, we systematically investigated Drosophila p24 proteins. We discovered that members of all four p24 subfamilies are required for general secretion and that their localizations between ER exit site (ERES) and Golgi are interdependent in an α→βδ→γ sequence...
May 6, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38451221/dux4-induced-hsatii-transcription-causes-kdm2a-b-prc1-nuclear-foci-and-impairs-dna-damage-response
#20
JOURNAL ARTICLE
Tessa Arends, Hiroshi Tsuchida, Richard O Adeyemi, Stephen J Tapscott
Polycomb repressive complexes regulate developmental gene programs, promote DNA damage repair, and mediate pericentromeric satellite repeat repression. Expression of pericentromeric satellite repeats has been implicated in several cancers and diseases, including facioscapulohumeral dystrophy (FSHD). Here, we show that DUX4-mediated transcription of HSATII regions causes nuclear foci formation of KDM2A/B-PRC1 complexes, resulting in a global loss of PRC1-mediated monoubiquitination of histone H2A. Loss of PRC1-ubiquitin signaling severely impacts DNA damage response...
May 6, 2024: Journal of Cell Biology
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