The role of HYAL2 in LSS-induced glycocalyx impairment and the PKA-mediated decrease in eNOS-Ser-633 phosphorylation and nitric oxide production.

Abstract:

:Hyaluronan (HA) in the endothelial glycocalyx serves as a mechanotransducer for high-shear-stress-stimulated endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production. Low shear stress (LSS) has been shown to contribute to endothelial inflammation and atherosclerosis by impairing the barrier and mechanotransduction properties of the glycocalyx. Here we focus on the possible role of hyaluronidase 2 (HYAL2) in LSS-induced glycocalyx impairment and the resulting alterations in eNOS phosphorylation and NO production in human umbilical vein endothelial cells (HUVECs). We show that LSS strongly activates HYAL2 to degrade HA in the glycocalyx. The dephosphorylation of eNOS-Ser-633 under LSS was triggered after HA degradation by hyaluronidase and prevented by repairing the glycocalyx with high-molecular weight hyaluronan. Knocking down HYAL2 in HUVECs protected against HA degradation in the glycocalyx by inhibiting the expression and activity of HYAL2 and further blocked the dephosphorylation of eNOS-Ser-633 and the decrease in NO production in response to LSS. The LSS-induced dephosphorylation of PKA was completely abrogated in HYAL2 siRNA-transfected HUVECs. The LSS-induced dephosphorylation of eNOS-Ser-633 was also reversed by the PKA activator 8-Br-cAMP. We thus suggest that LSS inhibits eNOS-Ser-633 phosphorylation and, at least partially, NO production by activating HYAL2 to degrade HA in the glycocalyx.

journal_name

Mol Biol Cell

authors

Kong X,Chen L,Ye P,Wang Z,Zhang J,Ye F,Chen S

doi

10.1091/mbc.E16-04-0241

subject

Has Abstract

pub_date

2016-12-15 00:00:00

pages

3972-3979

issue

25

eissn

1059-1524

issn

1939-4586

pii

mbc.E16-04-0241

journal_volume

27

pub_type

杂志文章
  • A Rab2 mutant with impaired GTPase activity stimulates vesicle formation from pre-Golgi intermediates.

    abstract::Rab2 immunolocalizes to pre-Golgi intermediates (vesicular-tubular clusters [VTCs]) that are the first site of segregation of anterograde- and retrograde-transported proteins and a major peripheral site for COPI recruitment. Our previous work showed that Rab2 Q65L (equivalent to Ras Q61L) inhibited endoplasmic reticul...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.10.6.1837

    authors: Tisdale EJ

    更新日期:1999-06-01 00:00:00

  • Cell cycle-dependent changes in microtubule dynamics in living cells expressing green fluorescent protein-alpha tubulin.

    abstract::LLCPK-1 cells were transfected with a green fluorescent protein (GFP)-alpha tubulin construct and a cell line permanently expressing GFP-alpha tubulin was established (LLCPK-1alpha). The mitotic index and doubling time for LLCPK-1alpha were not significantly different from parental cells. Quantitative immunoblotting s...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.12.4.971

    authors: Rusan NM,Fagerstrom CJ,Yvon AM,Wadsworth P

    更新日期:2001-04-01 00:00:00

  • A variable cytoplasmic domain segment is necessary for γ-protocadherin trafficking and tubulation in the endosome/lysosome pathway.

    abstract::Clustered protocadherins (Pcdhs) are arranged in gene clusters (α, β, and γ) with variable and constant exons. Variable exons encode cadherin and transmembrane domains and ~90 cytoplasmic residues. The 14 Pcdh-αs and 22 Pcdh-γs are spliced to constant exons, which, for Pcdh-γs, encode ~120 residues of an identical cyt...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-04-0283

    authors: O'Leary R,Reilly JE,Hanson HH,Kang S,Lou N,Phillips GR

    更新日期:2011-11-01 00:00:00

  • Time-varying mobility and turnover of actomyosin ring components during cytokinesis in Schizosaccharomyces pombe.

    abstract::Cytokinesis in many eukaryotes is dependent on a contractile actomyosin ring (AMR), composed of F-actin, myosin II, and other actin and myosin II regulators. Through fluorescence recovery after photobleaching experiments, many components of the AMR have been shown to be mobile and to undergo constant exchange with the...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E20-09-0588

    authors: Kamnev A,Palani S,Zambon P,Cheffings T,Burroughs N,Balasubramanian MK

    更新日期:2021-02-01 00:00:00

  • Detection of transient in vivo interactions between substrate and transporter during protein translocation into the endoplasmic reticulum.

    abstract::The split-ubiquitin technique was used to detect transient protein interactions in living cells. Nub, the N-terminal half of ubiquitin (Ub), was fused to Sec62p, a component of the protein translocation machinery in the endoplasmic reticulum of Saccharomyces cerevisiae. Cub, the C-terminal half of Ub, was fused to the...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.10.2.329

    authors: Dünnwald M,Varshavsky A,Johnsson N

    更新日期:1999-02-01 00:00:00

  • Signal transduction by the platelet integrin alpha IIb beta 3: induction of calcium oscillations required for protein-tyrosine phosphorylation and ligand-induced spreading of stably transfected cells.

    abstract::We demonstrate an example of signal transduction by an integrin and have begun to define the pathway through which this signaling is achieved. We constructed a stably transfected derivative of 293 cells (ATCC 1573) that expresses the platelet integrin GPIIbIIIa (alpha IIb beta 3). This cell line, clone B, adheres to a...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.3.9.989

    authors: Pelletier AJ,Bodary SC,Levinson AD

    更新日期:1992-09-01 00:00:00

  • Control of the spindle checkpoint by lateral kinetochore attachment and limited Mad1 recruitment.

    abstract::We observed the dynamic recruitment of spindle checkpoint proteins Mad1 and Bub1 to detached kinetochores in budding yeast using real-time live-cell imaging and quantified recruitment in fixed cells. After induced de novo kinetochore assembly at one pair of sister centromeres, Mad1 appeared after the kinetochore prote...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E15-05-0276

    authors: Krefman NI,Drubin DG,Barnes G

    更新日期:2015-07-15 00:00:00

  • Condensin suppresses recombination and regulates double-strand break processing at the repetitive ribosomal DNA array to ensure proper chromosome segregation during meiosis in budding yeast.

    abstract::During meiosis, homologues are linked by crossover, which is required for bipolar chromosome orientation before chromosome segregation at anaphase I. The repetitive ribosomal DNA (rDNA) array, however, undergoes little or no meiotic recombination. Hyperrecombination can cause chromosome missegregation and rDNA copy nu...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E14-05-0957

    authors: Li P,Jin H,Yu HG

    更新日期:2014-10-01 00:00:00

  • Physical interaction of calmodulin with the 5-hydroxytryptamine2C receptor C-terminus is essential for G protein-independent, arrestin-dependent receptor signaling.

    abstract::The serotonin (5-hydroxytryptamine; 5-HT)(2C) receptor is a G protein-coupled receptor (GPCR) exclusively expressed in CNS that has been implicated in numerous brain disorders, including anxio-depressive states. Like many GPCRs, 5-HT(2C) receptors physically interact with a variety of intracellular proteins in additio...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e08-04-0422

    authors: Labasque M,Reiter E,Becamel C,Bockaert J,Marin P

    更新日期:2008-11-01 00:00:00

  • Phosphorylation and internalization of gp130 occur after IL-6 activation of Jak2 kinase in hepatocytes.

    abstract::Recent evidence has shown that members of the Jak kinase family are activated after IL-6 binds to its receptor complex, leading to a tyrosine phosphorylation of gp130, the IL-6 signal-transducing subunit. The different members of the IL-6 cytokine subfamily induce distinct patterns of Jak-Tyk phosphorylation in differ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.5.7.819

    authors: Wang Y,Fuller GM

    更新日期:1994-07-01 00:00:00

  • The BNIP-2 and Cdc42GAP homology (BCH) domain of p50RhoGAP/Cdc42GAP sequesters RhoA from inactivation by the adjacent GTPase-activating protein domain.

    abstract::The BNIP-2 and Cdc42GAP homology (BCH) domain is a novel regulator for Rho GTPases, but its impact on p50-Rho GTPase-activating protein (p50RhoGAP or Cdc42GAP) in cells remains elusive. Here we show that deletion of the BCH domain from p50RhoGAP enhanced its GAP activity and caused drastic cell rounding. Introducing c...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E09-05-0408

    authors: Zhou YT,Chew LL,Lin SC,Low BC

    更新日期:2010-09-15 00:00:00

  • A role for calmodulin in organelle membrane tubulation.

    abstract::Membrane tubules of uniform diameter (60-80 nm) and variable lengths have been seen to extend from the main bodies of the Golgi complex, trans Golgi network (TGN), and endosomes. In the case of endosomes, these tubules appear to mediate membrane and receptor recycling events. Brefeldin A (BFA) is a potent drug that co...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.6.7.871

    authors: de Figueiredo P,Brown WJ

    更新日期:1995-07-01 00:00:00

  • Organization of the yeast Golgi complex into at least four functionally distinct compartments.

    abstract::Pro-alpha-factor (pro-alphaf) is posttranslationally modified in the yeast Golgi complex by the addition of alpha1,6-, alpha1,2-, and alpha1,3-linked mannose to N-linked oligosaccharides and by a Kex2p-initiated proteolytic processing event. Previous work has indicated that the alpha1,6- and alpha1,3-mannosylation and...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.11.1.171

    authors: Brigance WT,Barlowe C,Graham TR

    更新日期:2000-01-01 00:00:00

  • Identification of integrin beta subunit mutations that alter heterodimer function in situ.

    abstract::We conducted a genetic screen for mutations in myospheroid, the gene encoding the Drosophila betaPS integrin subunit, and identified point mutants in all of the structural domains of the protein. Surprisingly, we find that mutations in very strongly conserved residues will often allow sufficient integrin function to s...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-02-0085

    authors: Jannuzi AL,Bunch TA,West RF,Brower DL

    更新日期:2004-08-01 00:00:00

  • Enteropathogenic Escherichia coli subverts phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate upon epithelial cell infection.

    abstract::Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)] and phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P(3)] are phosphoinositides (PIs) present in small amounts in the inner leaflet of the plasma membrane (PM) lipid bilayer of host target cells. They are thought to modulate the activity of proteins involved in en...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e08-05-0516

    authors: Sason H,Milgrom M,Weiss AM,Melamed-Book N,Balla T,Grinstein S,Backert S,Rosenshine I,Aroeti B

    更新日期:2009-01-01 00:00:00

  • Ribosome-binding proteins Mdm38 and Mba1 display overlapping functions for regulation of mitochondrial translation.

    abstract::Biogenesis of respiratory chain complexes depends on the expression of mitochondrial-encoded subunits. Their synthesis occurs on membrane-associated ribosomes and is probably coupled to their membrane insertion. Defects in expression of mitochondrial translation products are among the major causes of mitochondrial dis...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e10-02-0101

    authors: Bauerschmitt H,Mick DU,Deckers M,Vollmer C,Funes S,Kehrein K,Ott M,Rehling P,Herrmann JM

    更新日期:2010-06-15 00:00:00

  • Aberrant Caveolin-1-Mediated Smad Signaling and Proliferation Identified by Analysis of Adenine 474 Deletion Mutation (c.474delA) in Patient Fibroblasts: A New Perspective in the Mechanism of Pulmonary Hypertension.

    abstract::A heterozygous Caveolin-1 c.474delA mutation has been identified in a family with heritable pulmonary arterial hypertension (PAH). This frameshift mutation leads to caveolin-1 protein that contains all known functional domains but has a change only in the final 20 amino acids of the C terminus. Here we studied how thi...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E16-06-0380

    authors: Marsboom G,Chen Z,Yuan Y,Zhang Y,Tiruppathi C,Loyd JE,Austin ED,Machado RF,Minshall RD,Rehman J,Malik AB

    更新日期:2017-03-15 00:00:00

  • Control of the mitotic exit network during meiosis.

    abstract::The mitotic exit network (MEN) is an essential GTPase signaling pathway that triggers exit from mitosis in budding yeast. We show here that during meiosis, the MEN is dispensable for exit from meiosis I but contributes to the timely exit from meiosis II. Consistent with a role for the MEN during meiosis II, we find th...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E12-03-0235

    authors: Attner MA,Amon A

    更新日期:2012-08-01 00:00:00

  • Fidgetin regulates cultured astrocyte migration by severing tyrosinated microtubules at the leading edge.

    abstract::Microtubule (MT) organization is essential for many cellular events, including mitosis, migration, and cell polarity. Fidgetin (Fign), an ATP-dependent, MT-severing protein, contributes to the regulation of MT configuration by cutting and trimming MT polymers. Functions of Fign have been indicated in neurite outgrowth...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E16-09-0628

    authors: Hu Z,Feng J,Bo W,Wu R,Dong Z,Liu Y,Qiang L,Liu M

    更新日期:2017-02-15 00:00:00

  • Monoubiquitination of syntaxin 3 leads to retrieval from the basolateral plasma membrane and facilitates cargo recruitment to exosomes.

    abstract::Syntaxin 3 (Stx3), a SNARE protein located and functioning at the apical plasma membrane of epithelial cells, is required for epithelial polarity. A fraction of Stx3 is localized to late endosomes/lysosomes, although how it traffics there and its function in these organelles is unknown. Here we report that Stx3 underg...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E17-07-0461

    authors: Giovannone AJ,Reales E,Bhattaram P,Fraile-Ramos A,Weimbs T

    更新日期:2017-10-15 00:00:00

  • An Amish founder mutation disrupts a PI(3)P-WHAMM-Arp2/3 complex-driven autophagosomal remodeling pathway.

    abstract::Actin nucleation factors function to organize, shape, and move membrane-bound organelles, yet they remain poorly defined in relation to disease. Galloway-Mowat syndrome (GMS) is an inherited disorder characterized by microcephaly and nephrosis resulting from mutations in the WDR73 gene. This core clinical phenotype ap...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E17-01-0022

    authors: Mathiowetz AJ,Baple E,Russo AJ,Coulter AM,Carrano E,Brown JD,Jinks RN,Crosby AH,Campellone KG

    更新日期:2017-09-15 00:00:00

  • Early stages of the secretory pathway, but not endosomes, are required for Cvt vesicle and autophagosome assembly in Saccharomyces cerevisiae.

    abstract::The Cvt pathway is a biosynthetic transport route for a distinct subset of resident yeast vacuolar hydrolases, whereas macroautophagy is a nonspecific degradative mechanism that allows cell survival during starvation. Yet, these two vacuolar trafficking pathways share a number of identical molecular components and are...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e03-07-0479

    authors: Reggiori F,Wang CW,Nair U,Shintani T,Abeliovich H,Klionsky DJ

    更新日期:2004-05-01 00:00:00

  • The Arp2/3 complex has essential roles in vesicle trafficking and transcytosis in the mammalian small intestine.

    abstract::The Arp2/3 complex is the only known nucleator of branched F-actin filaments. Work in cultured cells has established a wide array of functions for this complex in controlling cell migration, shape, and adhesion. However, loss of Arp2/3 complex function in tissues has yielded cell type-specific phenotypes. Here we repo...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E14-10-1481

    authors: Zhou K,Sumigray KD,Lechler T

    更新日期:2015-06-01 00:00:00

  • The role of the Src homology domains in morphological transformation by v-src.

    abstract::The Src homology (SH2 and SH3) domains of v-Src are required for transformation of Rat-2 cells and for wild-type (morphr) transformation of chicken embryo fibroblasts (CEFs). We report herein that the N-terminal domains of v-Src, when expressed in trans, cannot complement the transformation defect of a deletion mutant...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.8.7.1183

    authors: Tian M,Martin GS

    更新日期:1997-07-01 00:00:00

  • Dissociation of the tubulin-sequestering and microtubule catastrophe-promoting activities of oncoprotein 18/stathmin.

    abstract::Oncoprotein 18/stathmin (Op18) has been identified recently as a protein that destabilizes microtubules, but the mechanism of destabilization is currently controversial. Based on in vitro microtubule assembly assays, evidence has been presented supporting conflicting destabilization models of either tubulin sequestrat...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.10.1.105

    authors: Howell B,Larsson N,Gullberg M,Cassimeris L

    更新日期:1999-01-01 00:00:00

  • The tomosyn homologue, Sro7, is a direct effector of the Rab GTPase, Sec4, in post-Golgi vesicle tethering.

    abstract::The tomosyn/Sro7 family is thought to play an important role in cell surface trafficking both as an effector of Rab family GTPases and as a regulator of plasma-membrane SNARE function. Recent work has determined the binding site of GTP-bound Sec4 on Sro7. Here we examine the effect of mutations in Sro7 that block Sec4...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E18-02-0138

    authors: Rossi G,Watson K,Kennedy W,Brennwald P

    更新日期:2018-06-15 00:00:00

  • Transforming growth factor-beta complexes with thrombospondin.

    abstract::Thrombospondin (TSP) was demonstrated to inhibit the growth of bovine aortic endothelial cells, an activity that was not neutralized by antibodies to TSP or by other agents that block TSP-cell interactions but that partially was reversed by a neutralizing antibody to transforming growth factor-beta (TGF-beta). Similar...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.3.2.181

    authors: Murphy-Ullrich JE,Schultz-Cherry S,Höök M

    更新日期:1992-02-01 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

  • An interdomain binding site on HIV-1 Nef interacts with PACS-1 and PACS-2 on endosomes to down-regulate MHC-I.

    abstract::The human immunodeficiency virus type 1 (HIV-1) accessory protein Nef directs virus escape from immune surveillance by subverting host cell intracellular signaling and membrane traffic to down-regulate cell-surface major histocompatibility complex class I (MHC-I). The interaction of Nef with the sorting proteins PACS-...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-11-0928

    authors: Dikeakos JD,Thomas L,Kwon G,Elferich J,Shinde U,Thomas G

    更新日期:2012-06-01 00:00:00

  • Mechanistic insights into actin-driven polarity site movement in yeast.

    abstract::Directed cell growth or migration are critical for the development and function of many eukaryotic cells. These cells develop a dynamic "front" (also called "polarity site") that can change direction. Polarity establishment involves autocatalytic accumulation of polarity regulators, including the conserved Rho-family ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E20-01-0040

    authors: Ghose D,Lew D

    更新日期:2020-05-01 00:00:00