Identification of PTPsigma as an autophagic phosphatase.

Abstract:

:Macroautophagy is a dynamic process whereby portions of the cytosol are encapsulated in double-membrane vesicles and delivered to the lysosome for degradation. Phosphatidylinositol-3-phosphate (PtdIns3P) is concentrated on autophagic vesicles and recruits effector proteins that are crucial for this process. The production of PtdIns3P by the class III phosphatidylinositol 3-kinase Vps34, has been well established; however, protein phosphatases that antagonize this early step in autophagy remain to be identified. To identify such enzymes, we screened human phosphatase genes by RNA interference and found that loss of PTPσ, a dual-domain protein tyrosine phosphatase (PTP), increases levels of cellular PtdIns3P. The abundant PtdIns3P-positive vesicles conferred by loss of PTPσ strikingly phenocopied those observed in cells starved of amino acids. Accordingly, we discovered that loss of PTPσ hyperactivates both constitutive and induced autophagy. Finally, we found that PTPσ localizes to PtdIns3P-positive membranes in cells, and this vesicular localization is enhanced during autophagy. We therefore describe a novel role for PTPσ and provide insight into the regulation of autophagy. Mechanistic knowledge of this process is crucial for understanding and targeting therapies for several human diseases, including cancer and Alzheimer's disease, in which abnormal autophagy might be pathological.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Martin KR,Xu Y,Looyenga BD,Davis RJ,Wu CL,Tremblay ML,Xu HE,MacKeigan JP

doi

10.1242/jcs.080341

subject

Has Abstract

pub_date

2011-03-01 00:00:00

pages

812-9

issue

Pt 5

eissn

0021-9533

issn

1477-9137

pii

jcs.080341

journal_volume

124

pub_type

杂志文章
  • Dynamic resolution of acrosomal exocytosis in human sperm.

    abstract::An essential step in mammalian fertilisation is the sperm acrosome reaction (AR) - exocytosis of a single large vesicle (the acrosome) that surrounds the nucleus at the apical sperm head. The acrosomal and plasma membranes fuse, resulting in both the release of factors that might facilitate penetration of the zona pel...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:10.1242/jcs.030379

    authors: Harper CV,Cummerson JA,White MR,Publicover SJ,Johnson PM

    更新日期:2008-07-01 00:00:00

  • The cytostome-cytopharynx complex of Trypanosoma cruzi epimastigotes disassembles during cell division.

    abstract::The cytostome-cytopharynx complex is the main site for endocytosis in epimastigotes of Trypanosoma cruzi It consists of an opening at the plasma membrane surface - the cytostome - followed by a membrane invagination - the cytopharynx. In G1/S cells, this structure is associated with two specific sets of microtubules, ...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:10.1242/jcs.187419

    authors: Alcantara CL,Vidal JC,de Souza W,Cunha-E-Silva NL

    更新日期:2017-01-01 00:00:00

  • The integral function of the endocytic recycling compartment is regulated by RFFL-mediated ubiquitylation of Rab11 effectors.

    abstract::Endocytic trafficking is regulated by ubiquitylation (also known as ubiquitination) of cargoes and endocytic machineries. The role of ubiquitylation in lysosomal delivery has been well documented, but its role in the recycling pathway is largely unknown. Here, we report that the ubiquitin (Ub) ligase RFFL regulates ub...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:10.1242/jcs.228007

    authors: Sakai R,Fukuda R,Unida S,Aki M,Ono Y,Endo A,Kusumi S,Koga D,Fukushima T,Komada M,Okiyoneda T

    更新日期:2019-02-07 00:00:00

  • Cultured microvascular endothelial cells (MVEC) differ in cytoskeleton, expression of cadherins and fibronectin matrix. A study under the influence of interferon-gamma.

    abstract::Endothelial cells are known to undergo transitions in cell shape during long-term culture. Thus, the assumption that the separate phenotypes of microvascular endothelial cells (MVEC) recently isolated from bovine corpus luteum represent constitutively different cell strains cannot automatically be made. For this reaso...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:

    authors: Fenyves AM,Behrens J,Spanel-Borowski K

    更新日期:1993-11-01 00:00:00

  • Molecular probing of the secretory pathway in peptide hormone-producing cells.

    abstract::The biosynthetic machinery in the melanotrope cells of the Xenopus intermediate pituitary is primarily dedicated to the generation of proopiomelanocortin (POMC)-derived, melanophore-stimulating peptides. Transfer of the animal to a black background stimulates the production of these peptides and causes a dramatic incr...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:

    authors: Holthuis JC,Jansen EJ,van Riel MC,Martens GJ

    更新日期:1995-10-01 00:00:00

  • Effect of isolated plasma membranes on cell cohesion in the cellular slime mould.

    abstract::The effects of isolated plasma membranes on cohesion of Dictyostelium discoideum Ax-2 cells have been studied. Membranes isolated from cells in the log phase of growth gave complete inhibition of log-phase cell cohesion. This effect was specific for the cohesion log-phase cells mediated by contact sites B, since the c...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:

    authors: Jaffé AR,Garrod DR

    更新日期:1979-12-01 00:00:00

  • Mechanisms of Cx43 and Cx26 transport to the plasma membrane and gap junction regeneration.

    abstract::Previous reports have suggested that Cx26 exhibits unique intracellular transport pathways en route to the cell surface compared with other members of the connexin family. To directly examine and compare nascent and steady-state delivery of Cx43 and Cx26 to the plasma membrane and gap junction biogenesis we expressed ...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:10.1242/jcs.02569

    authors: Thomas T,Jordan K,Simek J,Shao Q,Jedeszko C,Walton P,Laird DW

    更新日期:2005-10-01 00:00:00

  • cdc2 kinase-induced destabilization of MAP2-coated microtubules in Xenopus egg extracts.

    abstract::During the interphase to metaphase transition, microtubules are destabilized by a cdc2 kinase-dependent phosphorylation event. This destabilization is due to a dramatic increase in the rate at which each growing microtubule starts to shrink (catastrophe rate). In principle, this could be brought about by lowering the ...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:

    authors: Faruki S,Dorée M,Karsenti E

    更新日期:1992-01-01 00:00:00

  • Distribution of desmosomal proteins in F9 embryonal carcinoma cells and epithelial cell derivatives.

    abstract::In diverse epithelia, cytoskeletal keratin intermediate filaments (IFs) associated with the cytoplasmic face of intercellular junctional desmosomes. The processes underlying desmosome formation and keratin IF interactions remain unclear. We have examined F9 embryonal carcinoma (EC) cell differentiation as a model for ...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:

    authors: Trevor KT,Steben LS

    更新日期:1992-09-01 00:00:00

  • Modulation of tight junction structure in blood-brain barrier endothelial cells. Effects of tissue culture, second messengers and cocultured astrocytes.

    abstract::Tight junctions between endothelial cells of brain capillaries are the most important structural elements of the blood-brain barrier. Cultured brain endothelial cells are known to loose tight junction-dependent blood-brain barrier characteristics such as macromolecular impermeability and high electrical resistance. We...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:

    authors: Wolburg H,Neuhaus J,Kniesel U,Krauss B,Schmid EM,Ocalan M,Farrell C,Risau W

    更新日期:1994-05-01 00:00:00

  • Src mediates the mechanical activation of myogenesis by activating TNFα-converting enzyme.

    abstract::Mechanical stimulation affects many biological aspects in living cells through mechanotransduction. In myogenic precursor cells (MPCs), mechanical stimulation activates p38 mitogen-activated protein kinase (MAPK), a key regulator of myogenesis, via activating TNFα-converting enzyme (TACE, also known as ADAM17), to rel...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:10.1242/jcs.125328

    authors: Niu A,Wen Y,Liu H,Zhan M,Jin B,Li YP

    更新日期:2013-10-01 00:00:00

  • Protein phosphatase 2A negatively regulates aPKC signaling by modulating phosphorylation of Par-6 in Drosophila neuroblast asymmetric divisions.

    abstract::Drosophila neural stem cells or neuroblasts undergo typical asymmetric cell division. An evolutionally conserved protein complex, comprising atypical protein kinase C (aPKC), Bazooka (Par-3) and Par-6, organizes cell polarity to direct these asymmetric divisions. Aurora-A (AurA) is a key molecule that links the divisi...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:10.1242/jcs.050955

    authors: Ogawa H,Ohta N,Moon W,Matsuzaki F

    更新日期:2009-09-15 00:00:00

  • Mitochondrial diacylglycerol initiates protein-kinase D1-mediated ROS signaling.

    abstract::Increases in reactive oxygen species (ROS) have been implicated in age-related diseases, including cancer. The serine/threonine kinase protein kinase D1 (PKD1) is a stress-responsive kinase and sensor for reactive oxygen species, which can initiate cell survival through NF-kappaB signaling. We have previously shown th...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:10.1242/jcs.041061

    authors: Cowell CF,Döppler H,Yan IK,Hausser A,Umezawa Y,Storz P

    更新日期:2009-04-01 00:00:00

  • RNA trafficking and stabilization elements associate with multiple brain proteins.

    abstract::Two of the best understood somatic cell mRNA cytoplasmic trafficking elements are those governing localization of beta-actin and myelin basic protein mRNAs. These cis-acting elements bind the trans-acting factors fibroblast ZBP-1 and hnRNP A2, respectively. It is not known whether these elements fulfil other roles in ...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:10.1242/jcs.00137

    authors: Snee M,Kidd GJ,Munro TP,Smith R

    更新日期:2002-12-01 00:00:00

  • The functions of anionic phospholipids during clathrin-mediated endocytosis site initiation and vesicle formation.

    abstract::Anionic phospholipids PI(4,5)P2 and phosphatidylserine (PS) are enriched in the cytosolic leaflet of the plasma membrane where endocytic sites form. In this study, we investigated the roles of PI(4,5)P2 and PS in clathrin-mediated endocytosis (CME) site initiation and vesicle formation in Saccharomyces cerevisiae. Liv...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:10.1242/jcs.115741

    authors: Sun Y,Drubin DG

    更新日期:2012-12-15 00:00:00

  • mTOR-dependent proliferation defect in human ES-derived neural stem cells affected by myotonic dystrophy type 1.

    abstract::Patients with myotonic dystrophy type 1 exhibit a diversity of symptoms that affect many different organs. Among these are cognitive dysfunctions, the origin of which has remained elusive, partly because of the difficulty in accessing neural cells. Here, we have taken advantage of pluripotent stem cell lines derived f...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:10.1242/jcs.116285

    authors: Denis JA,Gauthier M,Rachdi L,Aubert S,Giraud-Triboult K,Poydenot P,Benchoua A,Champon B,Maury Y,Baldeschi C,Scharfmann R,Piétu G,Peschanski M,Martinat C

    更新日期:2013-04-15 00:00:00

  • p53 is localized to a sub-nucleolar compartment after proteasomal inhibition in an energy-dependent manner.

    abstract::The tumor suppressor p53 is activated in response to many forms of cellular stress leading to cell cycle arrest, senescence or apoptosis. Appropriate sub-cellular localization is essential for modulating p53 function. We recently showed that p53 localizes to the nucleolus after proteasome inhibition with MG132 and thi...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:10.1242/jcs.030098

    authors: Karni-Schmidt O,Zupnick A,Castillo M,Ahmed A,Matos T,Bouvet P,Cordon-Cardo C,Prives C

    更新日期:2008-12-15 00:00:00

  • Events in the cytoplasm during male meiosis in Lilium.

    abstract::An electron microscopic investigation of the events associated with meiosis in Lilium has revealed a number of changes in both the organellar population and the other cytoplasmic components. Ribosome numbers decrease significantly in early prophase and are later replenished in the tetrads, a process most likely involv...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:

    authors: Bird J,Porter EK,Dickinson HG

    更新日期:1983-01-01 00:00:00

  • Cloned human teratoma cells differentiate into neuron-like cells and other cell types in retinoic acid.

    abstract::Single cell clones were isolated from the human teratoma line, Tera-2. The cells of three of these clones were studied. The progressively growing cells were shown to be tumorigenic, and they were characterized by the lack of expression of beta 2-microglobulin and HLA-A,B,C determinants on the cell surface. The majorit...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:

    authors: Thompson S,Stern PL,Webb M,Walsh FS,Engstrom W,Evans EP,Shi WK,Hopkins B,Graham CF

    更新日期:1984-12-01 00:00:00

  • CED-9 and mitochondrial homeostasis in C. elegans muscle.

    abstract::Mitochondrial homeostasis reflects a dynamic balance between membrane fission and fusion events thought essential for mitochondrial function. We report here that altered expression of the C. elegans BCL2 homolog CED-9 affects both mitochondrial fission and fusion. Although striated muscle cells lacking CED-9 have no a...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:10.1242/jcs.032904

    authors: Tan FJ,Husain M,Manlandro CM,Koppenol M,Fire AZ,Hill RB

    更新日期:2008-10-15 00:00:00

  • Expression of high molecular weight tau in the central and peripheral nervous systems.

    abstract::Using a novel PCR approach, we have cloned a cDNA encoding the entire high molecular weight tau molecule from rat dorsal root ganglia. The resulting 2080 bp cDNA differs from low molecular weight rat brain tau by the insertion of a novel 762 bp region (exon 4a) between exons 4 and 5. This cDNA clone is identical in se...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:

    authors: Georgieff IS,Liem RK,Couchie D,Mavilia C,Nunez J,Shelanski ML

    更新日期:1993-07-01 00:00:00

  • The C-terminal helix of BubR1 is essential for CENP-E-dependent chromosome alignment.

    abstract::During cell division, misaligned chromosomes are captured and aligned by motors before their segregation. The CENP-E motor is recruited to polar unattached kinetochores to facilitate chromosome alignment. The spindle checkpoint protein BubR1 (also known as BUB1B) has been reported as a CENP-E interacting partner, but ...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:10.1242/jcs.246025

    authors: Legal T,Hayward D,Gluszek-Kustusz A,Blackburn EA,Spanos C,Rappsilber J,Gruneberg U,Welburn JPI

    更新日期:2020-08-25 00:00:00

  • Identification of regulators of germ layer morphogenesis using proteomics in zebrafish.

    abstract::During vertebrate gastrulation, a well-orchestrated series of morphogenetic changes leads to the formation of the three germ layers: the ectoderm, mesoderm and endoderm. The analysis of gene expression patterns during gastrulation has been central to the identification of genes involved in germ layer formation. Howeve...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:10.1242/jcs.02928

    authors: Link V,Carvalho L,Castanon I,Stockinger P,Shevchenko A,Heisenberg CP

    更新日期:2006-05-15 00:00:00

  • The C-terminal domain LLKIL motif of CXCR2 is required for ligand-mediated polarization of early signals during chemotaxis.

    abstract::HEK293 cells expressing wild-type CXCR2 recruit PH-Akt-GFP to the leading edge of the cell in response to chemokine. However, in cells expressing mutant CXCR2 defective in AP-2 and HIP binding, i.e. with a mutation in the LLKIL motif, PH-Akt-GFP does not localize to the leading edge in response to ligand. Inhibition o...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:10.1242/jcs.01398

    authors: Sai J,Fan GH,Wang D,Richmond A

    更新日期:2004-11-01 00:00:00

  • Vinculin acts as a sensor in lipid regulation of adhesion-site turnover.

    abstract::The dynamics of cell adhesion sites control cell morphology and motility. Adhesion-site turnover is thought to depend on the local availability of the acidic phospholipid phosphatidylinositol-4,5-bisphosphate (PIP(2)). PIP(2) can bind to many cell adhesion proteins such as vinculin and talin, but the consequences of t...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:10.1242/jcs.01734

    authors: Chandrasekar I,Stradal TE,Holt MR,Entschladen F,Jockusch BM,Ziegler WH

    更新日期:2005-04-01 00:00:00

  • The presence or absence of a vimentin-type intermediate filament network affects the shape of the nucleus in human SW-13 cells.

    abstract::Human SW-13 cells express the intermediate filament protein vimentin in a mosaic pattern (Hedberg, K. K. and Chen, L. B. (1986). Exp. Cell Res. 163, 509-517). We have isolated SW-13 clones that do (vim+) or do not (vim-) synthesize vimentin as analyzed using anti-intermediate filament immunofluorescence, electron micr...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:

    authors: Sarria AJ,Lieber JG,Nordeen SK,Evans RM

    更新日期:1994-06-01 00:00:00

  • The distinct interaction between cell cycle regulation and the widely conserved morphogenesis-related (MOR) pathway in the fungus Ustilago maydis determines morphology.

    abstract::The morphogenesis-related NDR kinase (MOR) pathway regulates morphogenesis in fungi. In spite of the high conservation of its components, impairing their functions results in highly divergent cellular responses depending on the fungal species. The reasons for such differences are unclear. Here we propose that the spec...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:10.1242/jcs.107862

    authors: Sartorel E,Pérez-Martín J

    更新日期:2012-10-01 00:00:00

  • Coated vesicles from chicken liver bind ferritin.

    abstract::The iron-storage protein ferritin was found to be associated with highly purified coated vesicles (CV) from chicken liver. Chicken liver ferritin was morphologically similar to ferritin from horse spleen and could be isolated using a specific anti-ferritin monoclonal antibody. This antibody recognized a 240 X 10(3) Mr...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:

    authors: Passaniti A,Roth TF

    更新日期:1989-02-01 00:00:00

  • Mechanics of neutrophil phagocytosis: behavior of the cortical tension.

    abstract::The mechanical implementation of phagocytosis requires a well-coordinated deployment of cytoplasm and membrane during the creation of a phagosome. We follow the time course of this process in initially round passive neutrophils presented with antibody-coated beads of radii 1.1 to 5.5 microm. In particular, we monitor ...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:10.1242/jcs.02275

    authors: Herant M,Heinrich V,Dembo M

    更新日期:2005-05-01 00:00:00

  • Serotonin receptor oligomerization regulates cAMP-based signaling.

    abstract::Protein-protein interaction is often investigated using quantitative molecular microscopy with Förster resonant energy transfer (FRET). Here, we combined 'linear unmixing FRET' (lux-FRET) with the simultaneous application of a FRET-based biosensor for cAMP to investigate the oligomerization between the 5-HT7 receptor ...

    journal_title:Journal of cell science

    pub_type: 杂志文章

    doi:10.1242/jcs.230334

    authors: Prasad S,Ponimaskin E,Zeug A

    更新日期:2019-08-23 00:00:00