Journal: The Journal of Cell Biology

Abbreviation

J. Cell Biol.

Publisher

Rockefeller University Press

Journal Volumes

ISSN

0021-9525
1540-8140

Description

Filters

Reset filters

Search Results

Publications 1 - 10 of 86
  • Sem1 is a functional component of the nuclear pore complex–associated messenger RNA export machinery
    Item type: Journal Article
    Faza, Marius B.; Kemmler, Stefan; Jimeno, Sonia; et al. (2009)
    The Journal of Cell Biology
    The evolutionarily conserved protein Sem1/Dss1 is a subunit of the regulatory particle (RP) of the proteasome, and, in mammalian cells, binds the tumor suppressor protein BRCA2. Here, we describe a new function for yeast Sem1. We show that sem1 mutants are impaired in messenger RNA (mRNA) export and transcription elongation, and induce strong transcription-associated hyper-recombination phenotypes. Importantly, Sem1, independent of the RP, is functionally linked to the mRNA export pathway. Biochemical analyses revealed that, in addition to the RP, Sem1 coenriches with components of two other multisubunit complexes: the nuclear pore complex (NPC)-associated TREX-2 complex that is required for transcription-coupled mRNA export, and the COP9 signalosome, which is involved in deneddylation. Notably, targeting of Thp1, a TREX-2 component, to the NPC is perturbed in a sem1 mutant. These findings reveal an unexpected nonproteasomal function of Sem1 in mRNA export and in prevention of transcription-associated genome instability. Thus, Sem1 is a versatile protein that might stabilize multiple protein complexes involved in diverse pathways.
  • SORLA is required for insulin-induced expansion of the adipocyte precursor pool in visceral fat
    Item type: Journal Article
    Schmidt, Vanessa; Horváth, Carla; Dong, Hua; et al. (2021)
    The Journal of Cell Biology
    Visceral adipose tissue shows remarkable plasticity, constantly replacing mature adipocytes from an inherent pool of adipocyte precursors. The number of precursors is set in the juvenile organism and remains constant in adult life. Which signals drive precursor pool expansion in juveniles and why they operate in visceral but not in subcutaneous white adipose tissue (WAT) are unclear. Using mouse models, we identified the insulin-sensitizing receptor SORLA as a molecular factor explaining the distinct proliferative capacity of visceral WAT. High levels of SORLA activity in precursors of juvenile visceral WAT prime these cells for nutritional stimuli provided through insulin, promoting mitotic expansion of the visceral precursor cell pool in overfed juvenile mice. SORLA activity is low in subcutaneous precursors, blunting their response to insulin and preventing diet-induced proliferation of this cell type. Our findings provide a molecular explanation for the unique proliferative properties of juvenile visceral WAT, and for the genetic association of SORLA with visceral obesity in humans.
  • Hsp40/70/110 chaperones adapt nuclear protein quality control to serve cytosolic clients
    Item type: Journal Article
    Prasad, Rupali; Xu, Chengchao; Ng, Davis T. W. (2018)
    The Journal of Cell Biology
    Misfolded cytosolic proteins are degraded by the ubiquitin proteasome system through quality control (QC) pathways defined by E3 ubiquitin ligases and associated chaperones. Although they work together as a comprehensive system to monitor cytosolic protein folding, their respective contributions remain unclear. To bridge existing gaps, the pathways mediated by the San1 and Ubr1 E3 ligases were studied coordinately. We show that pathways share the same complement of chaperones needed for substrate trafficking, ubiquitination, and degradation. The significance became clear when Ubr1, like San1, was localized primarily to the nucleus. Appending nuclear localization signals to cytosolic substrates revealed that Ydj1 and Sse1 are needed for substrate nuclear import, whereas Ssa1/Ssa2 is needed both outside and inside the nucleus. Sis1 is required to process all substrates inside the nucleus, but its role in trafficking is substrate specific. Together, these data show that using chaperones to traffic misfolded cytosolic proteins into the nucleus extends the nuclear protein QC pathway to include cytosolic clients.
  • Different extracellular domains of neural cell adhesion molecule (N-CAM) are involved in different functions
    Item type: Journal Article
    Frei, Thomas; von Bohlen und Halbach, Friedrich; Wille, Wolfgang; et al. (1992)
    The Journal of Cell Biology
  • Mitotic control of kinetochore-associated dynein and spindle orientation by human Spindly
    Item type: Journal Article
    Chan, Ying Wai; Fava, Luca L.; Uldschmid, Andreas; et al. (2009)
    The Journal of Cell Biology
    Mitotic spindle formation and chromosome segregation depend critically on kinetochore–microtubule (KT–MT) interactions. A new protein, termed Spindly in Drosophila and SPDL-1 in C. elegans, was recently shown to regulate KT localization of dynein, but depletion phenotypes revealed striking differences, suggesting evolutionarily diverse roles of mitotic dynein. By characterizing the function of Spindly in human cells, we identify specific functions for KT dynein. We show that localization of human Spindly (hSpindly) to KTs is controlled by the Rod/Zw10/Zwilch (RZZ) complex and Aurora B. hSpindly depletion results in reduced inter-KT tension, unstable KT fibers, an extensive prometaphase delay, and severe chromosome misalignment. Moreover, depletion of hSpindly induces a striking spindle rotation, which can be rescued by co-depletion of dynein. However, in contrast to Drosophila, hSpindly depletion does not abolish the removal of MAD2 and ZW10 from KTs. Collectively, our data reveal hSpindly-mediated dynein functions and highlight a critical role of KT dynein in spindle orientation.
  • Neural crest-derived cells with stem cell features can be traced back to multiple lineages in the adult skin
    Item type: Journal Article
    Wong, Christine E.; Paratore, Christian; Dours-Zimmermann, María T.; et al. (2006)
    The Journal of Cell Biology
    Given their accessibility, multipotent skin-derived cells might be useful for future cell replacement therapies. We describe the isolation of multipotent stem cell–like cells from the adult trunk skin of mice and humans that express the neural crest stem cell markers p75 and Sox10 and display extensive self-renewal capacity in sphere cultures. To determine the origin of these cells, we genetically mapped the fate of neural crest cells in face and trunk skin of mouse. In whisker follicles of the face, many mesenchymal structures are neural crest derived and appear to contain cells with sphere-forming potential. In the trunk skin, however, sphere-forming neural crest–derived cells are restricted to the glial and melanocyte lineages. Thus, self-renewing cells in the adult skin can be obtained from several neural crest derivatives, and these are of distinct nature in face and trunk skin. These findings are relevant for the design of therapeutic strategies because the potential of stem and progenitor cells in vivo likely depends on their nature and origin.
  • 12R-lipoxygenase defi ciency disrupts epidermal barrier function
    Item type: Journal Article
    Epp, Nikolas; Fürstenberger, Gerhard; Müller, Karsten; et al. (2007)
    The Journal of Cell Biology
  • Tubulin polyglutamylation stimulates spastin-mediated microtubule severing
    Item type: Journal Article
    Lacroix, Benjamin; van Dijk, Juliette; Gold, Nicholas D.; et al. (2010)
    The Journal of Cell Biology
    Posttranslational glutamylation of tubulin is present on selected subsets of microtubules in cells. Although the modification is expected to contribute to the spatial and temporal organization of the cytoskeleton, hardly anything is known about its functional relevance. Here we demonstrate that glutamylation, and in particular the generation of long glutamate side chains, promotes the severing of microtubules. In human cells, the generation of long side chains induces spastin-dependent microtubule disassembly and, consistently, only microtubules modified by long glutamate side chains are efficiently severed by spastin in vitro. Our study reveals a novel control mechanism for microtubule mass and stability, which is of fundamental importance to cellular physiology and might have implications for diseases related to microtubule severing.
  • Computer vision profiling of neurite outgrowth dynamics reveals spatiotemporal modularity of Rho GTPase signaling
    Item type: Journal Article
    Fusco, Ludovico; Lefort, Riwal; Smith, Kevin; et al. (2016)
    The Journal of Cell Biology
    Rho guanosine triphosphatases (GTPases) control the cytoskeletal dynamics that power neurite outgrowth. This process consists of dynamic neurite initiation, elongation, retraction, and branching cycles that are likely to be regulated by specific spatiotemporal signaling networks, which cannot be resolved with static, steady-state assays. We present NeuriteTracker, a computer-vision approach to automatically segment and track neuronal morphodynamics in time-lapse datasets. Feature extraction then quantifies dynamic neurite outgrowth phenotypes. We identify a set of stereotypic neurite outgrowth morphodynamic behaviors in a cultured neuronal cell system. Systematic RNA interference perturbation of a Rho GTPase interactome consisting of 219 proteins reveals a limited set of morphodynamic phenotypes. As proof of concept, we show that loss of function of two distinct RhoA-specific GTPase-activating proteins (GAPs) leads to opposite neurite outgrowth phenotypes. Imaging of RhoA activation dynamics indicates that both GAPs regulate different spatiotemporal Rho GTPase pools, with distinct functions. Our results provide a starting point to dissect spatiotemporal Rho GTPase signaling networks that regulate neurite outgrowth.
  • Mitotic spindle (DIS)orientation and DISease: Cause or consequence?
    Item type: Review Article
    Noatynska, Anna; Gotta, Monica; Meraldi, Patrick (2012)
    The Journal of Cell Biology
    Correct alignment of the mitotic spindle during cell division is crucial for cell fate determination, tissue organization, and development. Mutations causing brain diseases and cancer in humans and mice have been associated with spindle orientation defects. These defects are thought to lead to an imbalance between symmetric and asymmetric divisions, causing reduced or excessive cell proliferation. However, most of these disease-linked genes encode proteins that carry out multiple cellular functions. Here, we discuss whether spindle orientation defects are the direct cause for these diseases, or just a correlative side effect.
Publications 1 - 10 of 86