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 Celljournal_title
Molecular biology of the cellauthors
Kong X,Chen L,Ye P,Wang Z,Zhang J,Ye F,Chen Sdoi
10.1091/mbc.E16-04-0241subject
Has Abstractpub_date
2016-12-15 00:00:00pages
3972-3979issue
25eissn
1059-1524issn
1939-4586pii
mbc.E16-04-0241journal_volume
27pub_type
杂志文章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
更新日期:1999-06-01 00:00:00
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
更新日期:2001-04-01 00:00:00
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
更新日期:2011-11-01 00:00:00
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
更新日期:2021-02-01 00:00:00
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
更新日期:1999-02-01 00:00:00
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
更新日期:1992-09-01 00:00:00
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
更新日期:2015-07-15 00:00:00
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
更新日期:2014-10-01 00:00:00
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
更新日期:2008-11-01 00:00:00
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
更新日期:1994-07-01 00:00:00
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
更新日期:2010-09-15 00:00:00
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
更新日期:1995-07-01 00:00:00
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
更新日期:2000-01-01 00:00:00
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
更新日期:2004-08-01 00:00:00
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
更新日期:2009-01-01 00:00:00
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
更新日期:2010-06-15 00:00:00
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
更新日期:2017-03-15 00:00:00
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
更新日期:2012-08-01 00:00:00
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
更新日期:2017-02-15 00:00:00
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
更新日期:2017-10-15 00:00:00
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
更新日期:2017-09-15 00:00:00
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
更新日期:2004-05-01 00:00:00
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
更新日期:2015-06-01 00:00:00
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
更新日期:1997-07-01 00:00:00
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
更新日期:1999-01-01 00:00:00
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
更新日期:2018-06-15 00:00:00
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
更新日期:1992-02-01 00:00:00
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
更新日期:1999-11-01 00:00:00
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
更新日期:2012-06-01 00:00:00
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
更新日期:2020-05-01 00:00:00