Up-regulation of BMP2/4 signaling increases both osteoblast-specific marker expression and bone marrow adipogenesis in Gja1Jrt/+ stromal cell cultures.

Abstract:

:Gja1(Jrt)/+ mice carry a mutation in one allele of the gap junction protein α1 gene (Gja1), resulting in a G60S connexin 43 (Cx43) mutant protein that is dominant negative for Cx43 protein production of <50% of wild-type (WT) levels and significantly reduced gap junction formation and function in osteoblasts and other Cx43-expressing cells. Previously we reported that Gja1(Jrt)/+ mice exhibited early-onset osteopenia caused by activation of osteoclasts secondary to activation of osteoblast lineage cells, which expressed increased RANKL and produced an abnormal resorption-stimulating bone matrix high in BSP content. Gja1(Jrt)/+ mice also displayed early and progressive bone marrow atrophy, with a significant increase in bone marrow adiposity versus WT littermates but no increase in adipose tissues elsewhere in the body. BMP2/4 production and signaling were increased in Gja1(Jrt)/+ trabecular bone and osteogenic stromal cell cultures, which contributed to the up-regulated expression of osteoblast-specific markers (e.g., Bsp and Ocn) in Gja1(Jrt)/+ osteoblasts and increased Pparg2 expression in bone marrow-derived adipoprogenitors in vitro. The elevated levels of BMP2/4 signaling in G60S Cx43-containing cells resulted at least in part from elevated levels of cAMP. We conclude that up-regulation of BMP2/4 signaling in trabecular bone and/or stromal cells increases osteoblast-specific marker expression in hyperactive Gja1(Jrt)/+ osteoblasts and may also increase bone marrow adipogenesis by up-regulation of Pparg2 in the Cx43-deficient Gja1(Jrt)/+ mouse model.

journal_name

Mol Biol Cell

authors

Zappitelli T,Chen F,Aubin JE

doi

10.1091/mbc.E14-06-1136

subject

Has Abstract

pub_date

2015-03-01 00:00:00

pages

832-42

issue

5

eissn

1059-1524

issn

1939-4586

pii

mbc.E14-06-1136

journal_volume

26

pub_type

杂志文章
  • Activation of androgen receptor function by a novel nuclear protein kinase.

    abstract::Androgen receptor (AR) belongs to the nuclear receptor superfamily and mediates the biological actions of male sex steroids. In this work, we have characterized a novel 130-kDa Ser/Thr protein kinase ANPK that interacts with the zinc finger region of AR in vivo and in vitro. The catalytic kinase domain of ANPK shares ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.9.9.2527

    authors: Moilanen AM,Karvonen U,Poukka H,Jänne OA,Palvimo JJ

    更新日期:1998-09-01 00:00:00

  • Identification of the endocytic sorting signal recognized by the Art1-Rsp5 ubiquitin ligase complex.

    abstract::Targeted endocytosis of plasma membrane (PM) proteins allows cells to adjust their complement of membrane proteins to changing extracellular conditions. For a wide variety of PM proteins, initiation of endocytosis is triggered by ubiquitination. In yeast, arrestin-related trafficking adaptors (ARTs) enable a single ub...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E16-08-0570

    authors: Guiney EL,Klecker T,Emr SD

    更新日期:2016-12-15 00:00:00

  • Activation of EGF receptor kinase by L1-mediated homophilic cell interactions.

    abstract::Neural cell adhesion molecules (CAMs) are important players during neurogenesis and neurite outgrowth as well as axonal fasciculation and pathfinding. Some of these developmental processes entail the activation of cellular signaling cascades. Pharmacological and genetic evidence indicates that the neurite outgrowth-pr...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e03-05-0333

    authors: Islam R,Kristiansen LV,Romani S,Garcia-Alonso L,Hortsch M

    更新日期:2004-04-01 00:00:00

  • Molecular mechanisms underlying cellular effects of human MEK1 mutations.

    abstract::Terminal regions of Drosophila embryos are patterned by signaling through ERK, which is genetically deregulated in multiple human diseases. Quantitative studies of terminal patterning have been recently used to investigate gain-of-function variants of human MEK1, encoding the MEK kinase that directly activates ERK by ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E20-10-0625

    authors: Marmion RA,Yang L,Goyal Y,Jindal GA,Wetzel JL,Singh M,Schüpbach T,Shvartsman SY

    更新日期:2021-01-21 00:00:00

  • c-Jun N-terminal kinase-mediated Rad18 phosphorylation facilitates Polη recruitment to stalled replication forks.

    abstract::The E3 ubiquitin ligase Rad18 chaperones DNA polymerase η (Polη) to sites of UV-induced DNA damage and monoubiquitinates proliferating cell nuclear antigen (PCNA), facilitating engagement of Polη with stalled replication forks and promoting translesion synthesis (TLS). It is unclear how Rad18 activities are coordinate...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-10-0829

    authors: Barkley LR,Palle K,Durando M,Day TA,Gurkar A,Kakusho N,Li J,Masai H,Vaziri C

    更新日期:2012-05-01 00:00:00

  • Association of ARVCF with zonula occludens (ZO)-1 and ZO-2: binding to PDZ-domain proteins and cell-cell adhesion regulate plasma membrane and nuclear localization of ARVCF.

    abstract::ARVCF, an armadillo-repeat protein of the p120(ctn) family, associates with classical cadherins and is present in adherens junctions, but its function is poorly understood. Here, we show that ARVCF interacts via a C-terminal PDZ-binding motif with zonula occludens (ZO)-1 and ZO-2. ARVCF and ZO-1 partially colocalize i...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-04-0350

    authors: Kausalya PJ,Phua DC,Hunziker W

    更新日期:2004-12-01 00:00:00

  • The zinc transporter ZnT3 interacts with AP-3 and it is preferentially targeted to a distinct synaptic vesicle subpopulation.

    abstract::Synaptic vesicles (SV) are generated by two different mechanisms, one AP-2 dependent and one AP-3 dependent. It has been uncertain, however, whether these mechanisms generate SV that differ in molecular composition. We explored this hypothesis by analyzing the targeting of ZnT3 and synaptophysin both to PC12 synaptic-...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e03-06-0401

    authors: Salazar G,Love R,Werner E,Doucette MM,Cheng S,Levey A,Faundez V

    更新日期:2004-02-01 00:00:00

  • Cloning and functional characterization of mammalian homologues of the COPII component Sec23.

    abstract::We screened a human cDNA library with a probe derived from a partial SEC23 mouse homologue and isolated two different cDNA clones (hSec23A and hSec23B) encoding proteins of a predicted molecular mass of 85 kDa. hSec23Ap and hSec23Bp were 85% identical and shared 48% identity with the yeast Sec23p. Affinity-purified an...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.7.10.1535

    authors: Paccaud JP,Reith W,Carpentier JL,Ravazzola M,Amherdt M,Schekman R,Orci L

    更新日期:1996-10-01 00:00:00

  • Transportin acts to regulate mitotic assembly events by target binding rather than Ran sequestration.

    abstract::The nuclear import receptors importin β and transportin play a different role in mitosis: both act phenotypically as spatial regulators to ensure that mitotic spindle, nuclear membrane, and nuclear pore assembly occur exclusively around chromatin. Importin β is known to act by repressing assembly factors in regions di...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E13-08-0506

    authors: Bernis C,Swift-Taylor B,Nord M,Carmona S,Chook YM,Forbes DJ

    更新日期:2014-04-01 00:00:00

  • Inhibition of Rho is required for cAMP-induced melanoma cell differentiation.

    abstract::Up-regulation of the cAMP pathway by forskolin or alpha-melanocyte stimulating hormone induces melanocyte and melanoma cell differentiation characterized by stimulation of melanin synthesis and dendrite development. Here we show that forskolin-induced dendricity is associated to a disassembly of actin stress fibers. S...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.9.6.1367

    authors: Buscà R,Bertolotto C,Abbe P,Englaro W,Ishizaki T,Narumiya S,Boquet P,Ortonne JP,Ballotti R

    更新日期:1998-06-01 00:00:00

  • Detyrosination of tubulin regulates the interaction of intermediate filaments with microtubules in vivo via a kinesin-dependent mechanism.

    abstract::Posttranslationally modified forms of tubulin accumulate in the subset of stabilized microtubules (MTs) in cells but are not themselves involved in generating MT stability. We showed previously that stabilized, detyrosinated (Glu) MTs function to localize vimentin intermediate filaments (IFs) in fibroblasts. To determ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.10.4.1105

    authors: Kreitzer G,Liao G,Gundersen GG

    更新日期:1999-04-01 00:00:00

  • Oxidative folding and assembly with transthyretin are sequential events in the biogenesis of retinol binding protein in the endoplasmic reticulum.

    abstract::Retinol-binding protein (RBP) is secreted out of the cell in its ligand-bound holo-form. The apo-form of RBP is selectively retained within the endoplasmic reticulum (ER) by a mechanism that remains unknown. Using isolated microsomal system, we have recapitulated the biogenesis of RBP involving its oxidative folding a...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e08-01-0026

    authors: Selvaraj SR,Bhatia V,Tatu U

    更新日期:2008-12-01 00:00:00

  • EB1 is essential during Drosophila development and plays a crucial role in the integrity of chordotonal mechanosensory organs.

    abstract::EB1 is a conserved microtubule plus end tracking protein considered to play crucial roles in microtubule organization and the interaction of microtubules with the cell cortex. Despite intense studies carried out in yeast and cultured cells, the role of EB1 in multicellular systems remains to be elucidated. Here, we de...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-07-0633

    authors: Elliott SL,Cullen CF,Wrobel N,Kernan MJ,Ohkura H

    更新日期:2005-02-01 00:00:00

  • Induction of S. cerevisiae filamentous differentiation by slowed DNA synthesis involves Mec1, Rad53 and Swe1 checkpoint proteins.

    abstract::A key question in eukaryotic differentiation is whether there are common regulators or biochemical events that are required for diverse types of differentiation or whether there is a core mechanism for differentiation. The unicellular model organism Saccharomyces cerevisiae undergoes filamentous differentiation in res...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e03-06-0375

    authors: Jiang YW,Kang CM

    更新日期:2003-12-01 00:00:00

  • The cAMP pathway regulates mRNA decay through phosphorylation of the RNA-binding protein TIS11b/BRF1.

    abstract::TPA-inducible sequence 11b/butyrate response factor 1 (TIS11b/BRF1) belongs to the tristetraprolin (TTP) family of zinc-finger proteins, which bind to mRNAs containing AU-rich elements in their 3'-untranslated region and target them for degradation. Regulation of TTP family function through phosphorylation by p38 MAP ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E16-06-0379

    authors: Rataj F,Planel S,Desroches-Castan A,Le Douce J,Lamribet K,Denis J,Feige JJ,Cherradi N

    更新日期:2016-12-01 00:00:00

  • Repositioning of muscle-specific genes relative to the periphery of SC-35 domains during skeletal myogenesis.

    abstract::Previous studies have shown that in a given cell type, certain active genes associate with SC-35 domains, nuclear regions rich in RNA metabolic factors and excluded from heterochromatin. This organization is not seen for all active genes; therefore, it is important to determine whether and when this locus-specific org...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e03-06-0388

    authors: Moen PT Jr,Johnson CV,Byron M,Shopland LS,de la Serna IL,Imbalzano AN,Lawrence JB

    更新日期:2004-01-01 00:00:00

  • Long-distance relationships: do membrane nanotubes regulate cell-cell communication and disease progression?

    abstract::Metazoan cells rapidly exchange signals at tight cell-cell interfaces, including synapses and gap junctions. Advances in imaging recently exposed a third mode of intercellular cross-talk mediated by thin, actin-containing membrane extensions broadly known as "membrane" or "tunneling" nanotubes. An explosion of researc...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E12-08-0622

    authors: Sherer NM

    更新日期:2013-04-01 00:00:00

  • Dual function of the NDR-kinase Dbf2 in the regulation of the F-BAR protein Hof1 during cytokinesis.

    abstract::The conserved NDR-kinase Dbf2 plays a critical role in cytokinesis in budding yeast. Among its cytokinesis-related substrates is the F-BAR protein Hof1. Hof1 colocalizes at the cell division site with the septin complex and, as mitotic exit progresses, moves to the actomyosin ring (AMR). Neither the function of Hof1 a...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E12-08-0608

    authors: Meitinger F,Palani S,Hub B,Pereira G

    更新日期:2013-05-01 00:00:00

  • Mammalian septins are required for phagosome formation.

    abstract::Septins are members of a highly conserved family of filamentous proteins that are required in many organisms for the completion of cytokinesis. In addition, septins have been implicated in a number of important cellular processes and have been suggested to have roles in regulating membrane traffic. Given the proposed ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-07-0641

    authors: Huang YW,Yan M,Collins RF,Diciccio JE,Grinstein S,Trimble WS

    更新日期:2008-04-01 00:00:00

  • Gamma-tubulin and the C-terminal motor domain kinesin-like protein, KLPA, function in the establishment of spindle bipolarity in Aspergillus nidulans.

    abstract::Previous research has found that a gamma-tubulin mutation in Schizosaccharomyces pombe is synthetically lethal with a deletion of the C-terminal motor domain kinesin-like protein gene pkl1, but the lethality of the double mutant prevents a phenotypic analysis of the synthetic interaction. We have investigated interact...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.12.10.3161

    authors: Prigozhina NL,Walker RA,Oakley CE,Oakley BR

    更新日期:2001-10-01 00:00:00

  • Calponin 3 regulates actin cytoskeleton rearrangement in trophoblastic cell fusion.

    abstract::Cell-cell fusion is an intriguing differentiation process, essential for placental development and maturation. A proteomic approach identified a cytoplasmic protein, calponin 3 (CNN3), related to the fusion of BeWo choriocarcinoma cells. CNN3 was expressed in cytotrophoblasts in human placenta. CNN3 gene knockdown pro...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E10-03-0261

    authors: Shibukawa Y,Yamazaki N,Kumasawa K,Daimon E,Tajiri M,Okada Y,Ikawa M,Wada Y

    更新日期:2010-11-15 00:00:00

  • GRIM-19 is essential for maintenance of mitochondrial membrane potential.

    abstract::GRIM-19 was found to copurify with complex I of mitochondrial respiratory chain and subsequently was demonstrated to be involved in complex I assembly and activity. To further understand its function in complex I, we dissected its functional domains by generating a number of deletion, truncation, and point mutants. Th...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-07-0683

    authors: Lu H,Cao X

    更新日期:2008-05-01 00:00:00

  • An Lsm2-Lsm7 complex in Saccharomyces cerevisiae associates with the small nucleolar RNA snR5.

    abstract::Sm-like (Lsm) proteins function in a variety of RNA-processing events. In yeast, the Lsm2-Lsm8 complex binds and stabilizes the spliceosomal U6 snRNA, whereas the Lsm1-Lsm7 complex functions in mRNA decay. Here we report that a third Lsm complex, consisting of Lsm2-Lsm7 proteins, associates with snR5, a box H/ACA snoR...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-02-0116

    authors: Fernandez CF,Pannone BK,Chen X,Fuchs G,Wolin SL

    更新日期:2004-06-01 00:00:00

  • Peroxisomal membrane proteins contain common Pex19p-binding sites that are an integral part of their targeting signals.

    abstract::Targeting of peroxisomal membrane proteins (PMPs) is a multistep process that requires not only recognition of PMPs in the cytosol but also their insertion into the peroxisomal membrane. As a consequence, targeting signals of PMPs (mPTS) are rather complex. A candidate protein for the PMP recognition event is Pex19p, ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-03-0188

    authors: Rottensteiner H,Kramer A,Lorenzen S,Stein K,Landgraf C,Volkmer-Engert R,Erdmann R

    更新日期:2004-07-01 00:00:00

  • ATP-dependent membrane assembly of F-actin facilitates membrane fusion.

    abstract::We recently established an in vitro assay that monitors the fusion between latex-bead phagosomes and endocytic organelles in the presence of J774 macrophage cytosol (). Here, we show that different reagents affecting the actin cytoskeleton can either inhibit or stimulate this fusion process. Because the membranes of p...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.12.1.155

    authors: Jahraus A,Egeberg M,Hinner B,Habermann A,Sackman E,Pralle A,Faulstich H,Rybin V,Defacque H,Griffiths G

    更新日期:2001-01-01 00:00:00

  • RNA polymerase III in Cajal bodies and lampbrush chromosomes of the Xenopus oocyte nucleus.

    abstract::We used immunofluorescence to study the distribution and targeting of RNA polymerase (pol) III subunits and pol III transcription factors in the Xenopus laevis oocyte nucleus. Antibodies against several of these proteins stained Cajal bodies and approximately 90 specific sites on the lampbrush chromosomes. Some of the...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-05-0281

    authors: Murphy C,Wang Z,Roeder RG,Gall JG

    更新日期:2002-10-01 00:00:00

  • Identification of a mitotic Rac-GEF, Trio, that counteracts MgcRacGAP function during cytokinesis.

    abstract::The Rho GTPases RhoA and Rac1 function as master regulators of cytokinesis by controlling the actomyosin cytoskeleton. RhoA and Rac1 have to be respectively activated and inactivated at the division plane for cytokinesis to occur properly. The inactivation of Rac1 at the cleavage furrow is controlled by MgcRacGAP. How...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E14-06-1153

    authors: Cannet A,Schmidt S,Delaval B,Debant A

    更新日期:2014-12-15 00:00:00

  • Involvement of a Golgi-resident GPI-anchored protein in maintenance of the Golgi structure.

    abstract::The Golgi apparatus consists of a series of flattened cisternal membranes that are aligned in parallel to form stacks. Cytosolic-oriented Golgi-associated proteins have been identified that may coordinate or maintain the Golgi architecture. Here, we describe a novel GPI-anchored protein, Golgi-resident GPI-anchored pr...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e06-03-0236

    authors: Li X,Kaloyanova D,van Eijk M,Eerland R,van der Goot G,Oorschot V,Klumperman J,Lottspeich F,Starkuviene V,Wieland FT,Helms JB

    更新日期:2007-04-01 00:00:00

  • Synaptic vesicles form by budding from tubular extensions of sorting endosomes in PC12 cells.

    abstract::The putative role of sorting early endosomes (EEs) in synaptic-like microvesicle (SLMV) formation in the neuroendocrine PC12 cell line was investigated by quantitative immunoelectron microscopy. By BSA-gold internalization kinetics, four distinct endosomal subcompartments were distinguished: primary endocytic vesicles...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.10.12.4163

    authors: de Wit H,Lichtenstein Y,Geuze HJ,Kelly RB,van der Sluijs P,Klumperman J

    更新日期:1999-12-01 00:00:00

  • Psychosine-triggered endomitosis is modulated by membrane sphingolipids through regulation of phosphoinositide 4,5-bisphosphate production at the cleavage furrow.

    abstract::Endomitosis is a special type of mitosis in which only cytokinesis-the final step of the cell division cycle-is defective, resulting in polyploid cells. Although endomitosis is biologically important, its regulatory aspects remain elusive. Psychosine, a lysogalactosylceramide, prevents proper cytokinesis when suppleme...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E15-08-0555

    authors: Watanabe H,Okahara K,Naito-Matsui Y,Abe M,Go S,Inokuchi J,Okazaki T,Kobayashi T,Kozutsumi Y,Oka S,Takematsu H

    更新日期:2016-07-01 00:00:00