Wnt regulation: exploring Axin-Disheveled interactions and defining mechanisms by which the SCF E3 ubiquitin ligase is recruited to the destruction complex.

Abstract:

:Wnt signaling plays key roles in embryonic development and adult stem cell homeostasis and is altered in human cancer. Signaling is turned on and off by regulating stability of the effector β-catenin (β-cat). The multiprotein destruction complex binds and phosphorylates β-cat and transfers it to the SCF-TrCP E3-ubiquitin ligase for ubiquitination and destruction. Wnt signals act though Dishevelled to turn down the destruction complex, stabilizing β-cat. Recent work clarified underlying mechanisms, but important questions remain. We explore β-cat transfer from the destruction complex to the E3 ligase, and test models suggesting Dishevelled and APC2 compete for association with Axin. We find that Slimb/TrCP is a dynamic component of the destruction complex biomolecular condensate, while other E3 proteins are not. Recruitment requires Axin and not APC, and Axin's RGS domain plays an important role. We find that elevating Dishevelled levels in Drosophila embryos has paradoxical effects, promoting the ability of limiting levels of Axin to turn off Wnt signaling. When we elevate Dishevelled levels, it forms its own cytoplasmic puncta, but these do not recruit Axin. Superresolution imaging in mammalian cells raises the possibility that this may result by promoting Dishevelled:Dishevelled interactions at the expense of Dishevelled: Axin interactions when Dishevelled levels are high.

journal_name

Mol Biol Cell

authors

Schaefer KN,Pronobis MI,Williams CE,Zhang S,Bauer L,Goldfarb D,Yan F,Major MB,Peifer M

doi

10.1091/mbc.E19-11-0647

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

992-1014

issue

10

eissn

1059-1524

issn

1939-4586

journal_volume

31

pub_type

杂志文章
  • Dissection of combinatorial control by the Met4 transcriptional complex.

    abstract::Met4 is the transcriptional activator of the sulfur metabolic network in Saccharomyces cerevisiae. Lacking DNA-binding ability, Met4 must interact with proteins called Met4 cofactors to target promoters for transcription. Two types of DNA-binding cofactors (Cbf1 and Met31/Met32) recruit Met4 to promoters and one cofac...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e09-05-0420

    authors: Lee TA,Jorgensen P,Bognar AL,Peyraud C,Thomas D,Tyers M

    更新日期:2010-02-01 00:00:00

  • NuMA interaction with chromatin is vital for proper chromosome decondensation at the mitotic exit.

    abstract::NuMA is an abundant long coiled-coil protein that plays a prominent role in spindle organization during mitosis. In interphase, NuMA is localized to the nucleus and hypothesized to control gene expression and chromatin organization. However, because of the prominent mitotic phenotype upon NuMA loss, its precise functi...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E20-06-0415

    authors: Rajeevan A,Keshri R,Kapoor S,Kotak S

    更新日期:2020-10-15 00:00:00

  • VX-809 corrects folding defects in cystic fibrosis transmembrane conductance regulator protein through action on membrane-spanning domain 1.

    abstract::Cystic fibrosis (CF) is a fatal genetic disorder associated with defective hydration of lung airways due to the loss of chloride transport through the CF transmembrane conductance regulator protein (CFTR). CFTR contains two membrane-spanning domains (MSDs), two nucleotide-binding domains (NBDs), and a regulatory domai...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E13-05-0240

    authors: Ren HY,Grove DE,De La Rosa O,Houck SA,Sopha P,Van Goor F,Hoffman BJ,Cyr DM

    更新日期:2013-10-01 00:00:00

  • The RNA-binding protein HuD is required for GAP-43 mRNA stability, GAP-43 gene expression, and PKC-dependent neurite outgrowth in PC12 cells.

    abstract::The RNA-binding protein HuD binds to a regulatory element in the 3' untranslated region (3' UTR) of the GAP-43 mRNA. To investigate the functional significance of this interaction, we generated PC12 cell lines in which HuD levels were controlled by transfection with either antisense (pDuH) or sense (pcHuD) constructs....

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.11.9.3191

    authors: Mobarak CD,Anderson KD,Morin M,Beckel-Mitchener A,Rogers SL,Furneaux H,King P,Perrone-Bizzozero NI

    更新日期:2000-09-01 00:00:00

  • Sec24C/D-isoform-specific sorting of the preassembled ER-Golgi Q-SNARE complex.

    abstract::Secretory proteins are exported from the endoplasmic reticulum in COPII vesicles. SNARE proteins-core machinery for membrane fusion-are incorporated into COPII vesicles by direct interaction with Sec24. Here we report a novel mechanism for sorting of the ER-Golgi Q-SNAREs into COPII vesicles. Different mammalian Sec24...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E16-04-0229

    authors: Adolf F,Rhiel M,Reckmann I,Wieland FT

    更新日期:2016-09-01 00:00:00

  • Fission yeast sts1+ gene encodes a protein similar to the chicken lamin B receptor and is implicated in pleiotropic drug-sensitivity, divalent cation-sensitivity, and osmoregulation.

    abstract::The Schizosaccharomyces pombe sts1+ gene, identified by supersensitive mutations to a protein kinase inhibitor, staurosporine, was isolated by complementation by the use of a fission yeast genomic library. Nucleotide sequencing shows that the sts1+ gene encodes a 453 amino acid putative membrane-associated protein tha...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.3.3.263

    authors: Shimanuki M,Goebl M,Yanagida M,Toda T

    更新日期:1992-03-01 00:00:00

  • Efficient interaction between two GTPases allows the chloroplast SRP pathway to bypass the requirement for an SRP RNA.

    abstract::Cotranslational protein targeting to membranes is regulated by two GTPases in the signal recognition particle (SRP) and the SRP receptor; association between the two GTPases is slow and is accelerated 400-fold by the SRP RNA. Intriguingly, the otherwise universally conserved SRP RNA is missing in a novel chloroplast S...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-01-0037

    authors: Jaru-Ampornpan P,Chandrasekar S,Shan SO

    更新日期:2007-07-01 00:00:00

  • Partner choice during meiosis is regulated by Hop1-promoted dimerization of Mek1.

    abstract::Meiotic recombination differs from mitotic recombination in that DSBs are repaired using homologous chromosomes, rather than sister chromatids. This change in partner choice is due in part to a barrier to sister chromatid repair (BSCR) created by the meiosis-specific kinase, Mek1, in a complex with two other meiosis-s...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e05-05-0465

    authors: Niu H,Wan L,Baumgartner B,Schaefer D,Loidl J,Hollingsworth NM

    更新日期:2005-12-01 00:00:00

  • The interaction and colocalization of Sam68 with the splicing-associated factor YT521-B in nuclear dots is regulated by the Src family kinase p59(fyn).

    abstract::Alternative pre-mRNA splicing patterns can change an extracellular stimulus, but the signaling pathways leading to these changes are still poorly characterized. Here, we describe a tyrosine-phosphorylated nuclear protein, YT521-B, and show that it interacts with the nuclear transcriptosomal component scaffold attachme...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.10.11.3909

    authors: Hartmann AM,Nayler O,Schwaiger FW,Obermeier A,Stamm S

    更新日期:1999-11-01 00:00:00

  • Microphthalmia-associated transcription factor interactions with 14-3-3 modulate differentiation of committed myeloid precursors.

    abstract::The microphthalmia-associated transcription factor (MITF) is required for terminal osteoclast differentiation and is a target for signaling pathways engaged by colony stimulating factor (CSF)-1 and receptor-activator of nuclear factor-kappaB ligand (RANKL). Work presented here demonstrates that MITF can shuttle from c...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e06-05-0470

    authors: Bronisz A,Sharma SM,Hu R,Godlewski J,Tzivion G,Mansky KC,Ostrowski MC

    更新日期:2006-09-01 00:00:00

  • Coupling to substrate adhesions drives the maturation of muscle stress fibers into myofibrils within cardiomyocytes.

    abstract::Forces generated by heart muscle contraction must be balanced by adhesion to the extracellular matrix (ECM) and to other cells for proper heart function. Decades of data have suggested that cell-ECM adhesions are important for sarcomere assembly. However, the relationship between cell-ECM adhesions and sarcomeres asse...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E19-11-0652

    authors: Taneja N,Neininger AC,Burnette DT

    更新日期:2020-06-01 00:00:00

  • Selective inactivation of a Fas-associated death domain protein (FADD)-dependent apoptosis and autophagy pathway in immortal epithelial cells.

    abstract::Although evasion of apoptosis is thought to be required for the development of cancer, it is unclear which cell death pathways are evaded. We previously identified a novel epithelial cell death pathway that works in normal cells but is inactivated in tumor cells, implying that it may be targeted during tumor developme...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-10-0906

    authors: Thorburn J,Moore F,Rao A,Barclay WW,Thomas LR,Grant KW,Cramer SD,Thorburn A

    更新日期:2005-03-01 00:00:00

  • Cingulin regulates claudin-2 expression and cell proliferation through the small GTPase RhoA.

    abstract::In mouse embryoid bodies, mutation of the tight junction protein cingulin results in changes in gene expression. Here, we studied the function of cingulin using a gene silencing approach in Madin-Darby canine kidney (MDCK) cells. Cingulin-depleted cells show higher protein and mRNA levels of claudin-2 and ZO-3, increa...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e06-02-0122

    authors: Guillemot L,Citi S

    更新日期:2006-08-01 00:00:00

  • XGef mediates early CPEB phosphorylation during Xenopus oocyte meiotic maturation.

    abstract::Polyadenylation-induced translation is an important regulatory mechanism during metazoan development. During Xenopus oocyte meiotic progression, polyadenylation-induced translation is regulated by CPEB, which is activated by phosphorylation. XGef, a guanine exchange factor, is a CPEB-interacting protein involved in th...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-07-0585

    authors: Martínez SE,Yuan L,Lacza C,Ransom H,Mahon GM,Whitehead IP,Hake LE

    更新日期:2005-03-01 00:00:00

  • C-terminus of the P4-ATPase ATP8A2 functions in protein folding and regulation of phospholipid flippase activity.

    abstract::ATP8A2 is a P4-ATPase that flips phosphatidylserine and phosphatidylethanolamine across cell membranes. This generates membrane phospholipid asymmetry, a property important in many cellular processes, including vesicle trafficking. ATP8A2 deficiency causes severe neurodegenerative diseases. We investigated the role of...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E16-06-0453

    authors: Chalat M,Moleschi K,Molday RS

    更新日期:2017-02-01 00:00:00

  • Pyruvate carboxylase is an essential protein in the assembly of yeast peroxisomal oligomeric alcohol oxidase.

    abstract::Hansenula polymorpha ass3 mutants are characterized by the accumulation of inactive alcohol oxidase (AO) monomers in the cytosol, whereas other peroxisomal matrix proteins are normally activated and sorted to peroxisomes. These mutants also have a glutamate or aspartate requirement on minimal media. Cloning of the cor...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-07-0417

    authors: Ozimek P,van Dijk R,Latchev K,Gancedo C,Wang DY,van der Klei IJ,Veenhuis M

    更新日期:2003-02-01 00:00:00

  • SLC25A23 augments mitochondrial Ca²⁺ uptake, interacts with MCU, and induces oxidative stress-mediated cell death.

    abstract::Emerging findings suggest that two lineages of mitochondrial Ca(2+) uptake participate during active and resting states: 1) the major eukaryotic membrane potential-dependent mitochondrial Ca(2+) uniporter and 2) the evolutionarily conserved exchangers and solute carriers, which are also involved in ion transport. Alth...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E13-08-0502

    authors: Hoffman NE,Chandramoorthy HC,Shanmughapriya S,Zhang XQ,Vallem S,Doonan PJ,Malliankaraman K,Guo S,Rajan S,Elrod JW,Koch WJ,Cheung JY,Madesh M

    更新日期:2014-03-01 00:00:00

  • Compositional complexity of rods and rings.

    abstract::Rods and rings (RRs) are large linear- or circular-shaped structures typically described as polymers of IMPDH (inosine monophosphate dehydrogenase). They have been observed across a wide variety of cell types and species and can be induced to form by inhibitors of IMPDH. RRs are thought to play a role in the regulatio...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E18-05-0274

    authors: Schiavon CR,Griffin ME,Pirozzi M,Parashuraman R,Zhou W,Jinnah HA,Reines D,Kahn RA

    更新日期:2018-09-15 00:00:00

  • Changes in organization of the endoplasmic reticulum during Xenopus oocyte maturation and activation.

    abstract::The organization of the endoplasmic reticulum (ER) in the cortex of Xenopus oocytes was investigated during maturation and activation using a green fluorescent protein chimera, immunofluorescence, and electron microscopy. Dense clusters of ER developed on the vegetal side (the side opposite the meiotic spindle) during...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.12.4.1103

    authors: Terasaki M,Runft LL,Hand AR

    更新日期:2001-04-01 00:00:00

  • Palmitoylation of tetraspanin proteins: modulation of CD151 lateral interactions, subcellular distribution, and integrin-dependent cell morphology.

    abstract::Here we demonstrate that multiple tetraspanin (transmembrane 4 superfamily) proteins are palmitoylated, in either the Golgi or a post-Golgi compartment. Using CD151 as a model tetraspanin, we identified and mutated intracellular N-terminal and C-terminal cysteine palmitoylation sites. Simultaneous mutations of C11, C1...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.01-05-0275

    authors: Yang X,Claas C,Kraeft SK,Chen LB,Wang Z,Kreidberg JA,Hemler ME

    更新日期:2002-03-01 00:00:00

  • Biochemical and functional analysis of the YME1 gene product, an ATP and zinc-dependent mitochondrial protease from S. cerevisiae.

    abstract::Inactivation of YME1 in yeast causes several distinct phenotypes: an increased rate of DNA escape from mitochondria, temperature-sensitive growth on nonfermentable carbon sources, extremely slow growth when mitochondrial DNA is completely absent from the cell, and altered morphology of the mitochondrial compartment. T...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.7.2.307

    authors: Weber ER,Hanekamp T,Thorsness PE

    更新日期:1996-02-01 00:00:00

  • Amyloid-β oligomers induce tau-independent disruption of BDNF axonal transport via calcineurin activation in cultured hippocampal neurons.

    abstract::Disruption of fast axonal transport (FAT) is an early pathological event in Alzheimer's disease (AD). Soluble amyloid-β oligomers (AβOs), increasingly recognized as proximal neurotoxins in AD, impair organelle transport in cultured neurons and transgenic mouse models. AβOs also stimulate hyperphosphorylation of the ax...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E12-12-0858

    authors: Ramser EM,Gan KJ,Decker H,Fan EY,Suzuki MM,Ferreira ST,Silverman MA

    更新日期:2013-08-01 00:00:00

  • Interactions among Rax1p, Rax2p, Bud8p, and Bud9p in marking cortical sites for bipolar bud-site selection in yeast.

    abstract::In the budding yeast Saccharomyces cerevisiae, selection of the bud site determines the axis of polarized cell growth and eventual oriented cell division. Bud sites are selected in specific patterns depending on cell type. These patterns appear to depend on distinct types of marker proteins in the cell cortex; in part...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-07-0600

    authors: Kang PJ,Angerman E,Nakashima K,Pringle JR,Park HO

    更新日期:2004-11-01 00:00:00

  • Down-regulation of cell surface receptors is modulated by polar residues within the transmembrane domain.

    abstract::How recycling receptors are segregated from down-regulated receptors in the endosome is unknown. In previous studies, we demonstrated that substitutions in the transferrin receptor (TR) transmembrane domain (TM) convert the protein from an efficiently recycling receptor to one that is rapidly down regulated. In this s...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.11.8.2643

    authors: Zaliauskiene L,Kang S,Brouillette CG,Lebowitz J,Arani RB,Collawn JF

    更新日期:2000-08-01 00:00:00

  • Activated Cdc42-associated kinase 1 is a component of EGF receptor signaling complex and regulates EGF receptor degradation.

    abstract::Cdc42-associated tyrosine kinase 1 (ACK1) is a specific down-stream effector of Cdc42, a Rho family small G-protein. Previous studies have shown that ACK1 interacts with clathrin heavy chain and is involved in clathrin-coated vesicle endocytosis. Here we report that ACK1 interacted with epidermal growth factor recepto...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e06-02-0142

    authors: Shen F,Lin Q,Gu Y,Childress C,Yang W

    更新日期:2007-03-01 00:00:00

  • Cytoplasmic and nuclear phospholipase C-beta 1 relocation: role in resumption of meiosis in the mouse oocyte.

    abstract::The location of the phospholipase C beta 1-isoform (PLC-beta 1) in the mouse oocyte and its role in the resumption of meiosis were examined. We used specific monoclonal antibodies to monitor the in vitro dynamics of the subcellular distribution of the enzyme from the release of the oocyte from the follicle until break...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.11.12.4369

    authors: Avazeri N,Courtot AM,Pesty A,Duquenne C,Lefèvre B

    更新日期:2000-12-01 00:00:00

  • The heat-shock protein Apg-2 binds to the tight junction protein ZO-1 and regulates transcriptional activity of ZONAB.

    abstract::The tight junction adaptor protein ZO-1 regulates intracellular signaling and cell proliferation. Its Src homology 3 (SH3) domain is required for the regulation of proliferation and binds to the Y-box transcription factor ZO-1-associated nucleic acid binding protein (ZONAB). Binding of ZO-1 to ZONAB results in cytopla...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e05-06-0507

    authors: Tsapara A,Matter K,Balda MS

    更新日期:2006-03-01 00:00:00

  • p27Kip1 acts downstream of N-cadherin-mediated cell adhesion to promote myogenesis beyond cell cycle regulation.

    abstract::It is widely acknowledged that cultured myoblasts can not differentiate at very low density. Here we analyzed the mechanism through which cell density influences myogenic differentiation in vitro. By comparing the behavior of C2C12 myoblasts at opposite cell densities, we found that, when cells are sparse, failure to ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-07-0612

    authors: Messina G,Blasi C,La Rocca SA,Pompili M,Calconi A,Grossi M

    更新日期:2005-03-01 00:00:00

  • The RHO1-specific GTPase-activating protein LRG1 regulates polar tip growth in parallel to Ndr kinase signaling in Neurospora.

    abstract::Regulation of Rho GTPase signaling is critical for cell shape determination and polarity. Here, we investigated the role of LRG1, a novel member of the GTPase-activating proteins (GAPs) of Neurospora crassa. LRG1 is essential for apical tip extension and to restrict excessive branch formation in subapical regions of t...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-12-1266

    authors: Vogt N,Seiler S

    更新日期:2008-11-01 00:00:00

  • Rescue of Munc18-1 and -2 double knockdown reveals the essential functions of interaction between Munc18 and closed syntaxin in PC12 cells.

    abstract::Munc18-1 binds to syntaxin-1A via two distinct sites referred to as the "closed" conformation and N terminus binding. The latter has been shown to stimulate soluble N-ethylmaleimide-sensitive factor attachment protein receptor-mediated exocytosis, whereas the former is believed to be inhibitory or dispensable. To prec...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e09-08-0712

    authors: Han L,Jiang T,Han GA,Malintan NT,Xie L,Wang L,Tse FW,Gaisano HY,Collins BM,Meunier FA,Sugita S

    更新日期:2009-12-01 00:00:00