Abstract:
:Vascular tube morphogenesis requires the establishment of endothelial cell (EC) apical-basal polarity in three-dimensional (3D) extracellular matrices. To date, there is little understanding of how EC polarity is controlled during these highly dynamic and rapid morphogenic events. We show that the microtubule tip complex proteins, end binding 1 (EB1), p150(Glued), and Clasp1, control human EC tube formation by (1) inducing microtubule assembly and asymmetric cytoskeletal polarization, whereby acetylated and detyrosinated tubulins distribute in a subapical membrane location and filamentous actin distributes basally; (2) increasing tubulin posttranslational modifications, including required acetylation events; and (3) regulating an EC lumen signaling cascade that involves membrane type 1 matrix metallopatrinase (MT1-MMP)-dependent proteolysis as well as Pak, Raf, and Erk kinases. Another regulator of this process is the microtubule stabilizing protein, tau, which binds p150(Glued) and similarly affects EC lumen formation by controlling the levels of acetylated and detyrosinated tubulins. Increased expression of the tubulin deacetylases, sirtuin 2, and histone deacetylase 6 (HDAC6), blocks EC tube formation and cytoskeletal polarization, while siRNA suppression of these deacetylases stimulates these events. Overall, this work reveals a fundamental role for microtubule tip complex proteins in coordinating microtubule assembly, posttranslational modifications including acetylation, and apical-basal cytoskeletal polarization to control the developing apical membrane surface during blood vessel tubulogenesis in 3D matrix environments.
journal_name
Bloodjournal_title
Bloodauthors
Kim DJ,Martinez-Lemus LA,Davis GEdoi
10.1182/blood-2012-11-470179subject
Has Abstractpub_date
2013-04-25 00:00:00pages
3521-30issue
17eissn
0006-4971issn
1528-0020pii
blood-2012-11-470179journal_volume
121pub_type
杂志文章相关文献
BLOOD文献大全abstract::This study reports a lentiviral gene transfer protocol for efficient transduction of adult human peripheral blood (PB)-derived CD34+ NOD/SCID-repopulating cells (SRCs) using vesicular stomatitis virus-G protein (VSV-G)-pseudotyped lentiviruses encoding for enhanced green fluorescence protein (eGFP). Lentiviral stocks ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.2.709
更新日期:2002-01-15 00:00:00
abstract::Approximately 20% of children with acute lymphoblastic leukemia (ALL) relapse because of failure to eradicate the disease. Current drug efficacy studies focus on reducing leukemia cell burden. However, if drugs have limited effects on leukemia-initiating cells (LICs), then these cells may expand and eventually cause r...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-08-448852
更新日期:2013-02-21 00:00:00
abstract::Glycosaminoglycans (GAG) are a group of negatively charged molecules that have been shown to bind and directly regulate the bioactivity of growth factors and cytokines such as basic fibroblast growth factor, transforming growth factor-beta, IL-7, and interferon-gamma. The ability of GAG to interact with human IL-10 (h...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-09-01 00:00:00
abstract::T cell-depleted haploidentical hematopoietic stem cell transplantation (haploHSCT) is an option to treat children with very high-risk acute lymphoblastic leukemia (ALL) lacking an HLA-identical donor. We analyzed 127 children with ALL who underwent haploHSCT in first (n = 22), second (n = 48), or third (n = 32), compl...
journal_title:Blood
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1182/blood-2009-03-207001
更新日期:2010-04-29 00:00:00
abstract::The proteolytic cleavage and subsequent inactivation of recombinant human factor VIII (rhFVIII) and human factor VIIIa (rhFVIIIa) by recombinant human activated protein C (rAPC) was analyzed in the presence and absence of human protein S and human factor V (FV). Membrane-bound rhFVIIIa spontaneously looses most of its...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-06-01 00:00:00
abstract::We report on a second generation of transgenic mice produced by crossing a transgenic mouse line expressing high levels of human alpha and beta S chains (alpha H beta S [beta MDD]) with a line expressing human alpha and beta S-Antilles (beta SAnt). We hypothesized that mice expressing both hemoglobins (Hbs) would have...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-09-15 00:00:00
abstract::Ravulizumab (ALXN1210), a new complement C5 inhibitor, provides immediate, complete, and sustained C5 inhibition. This phase 3, open-label study assessed the noninferiority of ravulizumab to eculizumab in complement inhibitor-naive adults with paroxysmal nocturnal hemoglobinuria (PNH). Patients with lactate dehydrogen...
journal_title:Blood
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1182/blood-2018-09-876136
更新日期:2019-02-07 00:00:00
abstract::Optimal dose and timing of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy for aggressive non-Hodgkin lymphoma (NHL) is still an unresolved issue. We assessed whether dose intensifications with cyclophosphamide and doxorubicin might improve outcome in younger patients with intermediate-r...
journal_title:Blood
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1182/blood-2006-07-035709
更新日期:2007-04-01 00:00:00
abstract::Male recipients of transplants from female (F-->M) hematopoietic stem cell donors represent a special group in whom donor T cells that are specific for recipient minor histocompatibility antigens encoded by Y-chromosome genes may contribute to a graft-versus-leukemia (GVL) effect and to graft-versus-host disease (GVHD...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-07-2603
更新日期:2004-01-01 00:00:00
abstract::Ectopic expression of fibroblast growth factor receptor 3 (FGFR3) associated with t(4;14) has been implicated in the pathogenesis of human multiple myeloma. Some t(4;14) patients have activating mutations of FGFR3, of which a minority are K650E (thanatophoric dysplasia type II [TDII]). To investigate the role of autop...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-09-3686
更新日期:2005-07-01 00:00:00
abstract::Twenty consecutive patients with Hodgkin disease in continuous complete remission and off treatment for at least 5 yr (range 5-25 yr, median 9 yr) were studied with a battery of immunologic parameters. Skin test reactivity to four common antigens, sensitization to 2,4-dinitrochlorobenzene, absolute lymphocyte count, r...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1977-05-01 00:00:00
abstract::The adhesion of leukocytes to platelets deposited at the site of vascular injury may represent an important mechanism by which leukocytes contribute to hemostasis and thrombosis. In this study, we examined whether, in comparison with their distribution in circulating blood, certain leukocyte types are enriched at site...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-02-15 00:00:00
abstract::The lymphocytosis manifested in infectious mononucleosis (IM) during acute phase is ascribed to a reactive expansion of CD8+ T lymphocytes caused by Epstein-Barr virus (EBV)-infected B lymphocytes. Expression of HLA-DR antigen on IM lymphocytes suggests that these T lymphocytes are somehow activated in vivo. In the pr...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1990-01-15 00:00:00
abstract::Although combination regimens have improved outcomes over monotherapy in chronic lymphocytic leukemia (CLL), patients eventually relapse. Combined fludarabine, cyclophosphamide, and monoclonal anti-CD52 antibody alemtuzumab (FCC) provided synergistic cytotoxicity with effective clearing of minimal residual disease. Th...
journal_title:Blood
pub_type: 杂志文章,多中心研究
doi:10.1182/blood-2011-05-351833
更新日期:2011-10-13 00:00:00
abstract::Glycogen storage disease type 1b (GSD1b) is a rare autosomal recessive disorder characterized by hypoglycemia, hepatomegaly, and growth retardation, and associated-for unknown reasons- with neutropenia and neutrophil dysfunction. In 5 GSD1b patients in whom nicotin-amide adenine dinucleotide phosphate-oxidase activity...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-10-3128
更新日期:2003-06-15 00:00:00
abstract::Mesenchymal stem cells (MSCs) are widespread in adult organisms and may be involved in tissue maintenance and repair as well as in the regulation of hematopoiesis and immunologic responses. Thus, it is important to discover the factors controlling MSC renewal and differentiation. Here we report that adult MSCs express...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-06-028704
更新日期:2007-02-15 00:00:00
abstract::The synthetic cytokine (Synthokine) SC-55494 is a high-affinity interleukin-3 (IL-3) receptor ligand that stimulates greater in vitro multilineage hematopoietic activity than native IL-3, while inducing no significant increase in inflammatory activity relative to native IL-3. The aim of this study was to investigate t...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-01-15 00:00:00
abstract::Human granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances numerous functions of mature neutrophils (PMN) including phagocytosis, superoxide responses to chemotaxins, antibody-dependent cellular cytotoxicity, and expression of complement receptors. A central question concerns whether the mechanism of enh...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1988-03-01 00:00:00
abstract::Although sickle cell disease (SCD) has a variable clinical course, many patients develop end-organ complications that are associated with significant morbidity and early mortality. Myeloablative allogeneic HSCT (allo-HSCT) is curative but has been historically performed only in children younger than 16 years of age. M...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2011-01-332510
更新日期:2011-08-04 00:00:00
abstract::Efficient clearance of apoptotic cells seems to be a prerequisite to prevent the development of autoimmunity. Here we identify that macrophage colony-stimulating factor (M-CSF)-driven macrophages (Mø2s) are potent phagocytes that have the unique capacity to preferentially bind and ingest early apoptotic cells. This ma...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-10-4144
更新日期:2006-06-15 00:00:00
abstract::Age-associated clonal hematopoiesis caused by acquired mutations in myeloid cancer-associated genes is highly prevalent in the normal population. Its etiology, biological impact on hematopoiesis, and oncogenic risk is poorly defined at this time. To gain insight into this phenomenon, we analyzed a cohort of 2530 relat...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2017-04-777029
更新日期:2017-08-10 00:00:00
abstract::Gene therapy for hemophilia A requires efficient delivery of the factor VIII gene and sustained protein expression at circulating levels of at least 1% to 2% of normal. Adeno-associated viral type 2 (AAV2) vectors have a number of advantages over other viral vectors, including an excellent safety profile and persisten...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-01-0292
更新日期:2003-09-15 00:00:00
abstract::The transcription factor (TF) RUNX1 cooperates with lineage-specifying TFs (eg, PU.1/SPI1) to activate myeloid differentiation genes, such as macrophage and granulocyte macrophage colony-stimulating factor receptors (MCSFR and GMCSFR). Disruption of cooperative gene activation could contribute to aberrant repression o...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-10-312512
更新日期:2011-06-16 00:00:00
abstract::Repeated analysis of peripheral blood lymphocytes (PBLs) from a patient with large granular lymphocytosis, neutropenia, and rheumatoid arthritis revealed that approximately 45% of PBLs displayed the following phenotype: CD3+, CD4-, CD8-, CD16+, HNK-1-, WT31-. This population was purified for further analysis by deplet...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1989-07-01 00:00:00
abstract::Filamin A (FLNa), a dimeric actin cross-linking and scaffold protein with numerous intracellular binding partners, anchors the platelet adhesion glycoprotein (GP) Ib-IX-V receptor to actin cytoskeleton. We mapped the GPIbalpha binding site to a single domain of FLNa and resolved the structure of this domain and its in...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-10-3964
更新日期:2006-03-01 00:00:00
abstract::The functions of the alphaC domains of fibrinogen in clotting and fibrinolysis, which have long been enigmatic, were determined using recombinant fibrinogen truncated at Aalpha chain residue 251. Scanning electron microscopy and confocal microscopy revealed that the fibers of alpha251 clots were thinner and denser, wi...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-05-2150
更新日期:2005-12-01 00:00:00
abstract::Monoclonally-derived neoplastic T-cells from a patient with cutaneous T-cell lymphoma respond to multiple human HLA-D antigens in mixed lymphocyte culture. The implications of this phenomenon relevant to normal T-cell function and to malignancy are discussed. ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1980-03-01 00:00:00
abstract::The Wiskott-Aldrich syndrome (WAS) is a severe immunodeficiency and platelet deficiency disease arising from mutation(s) in the WASP gene, which in normal cells encodes an intracellular protein able to interact with other proteins relevant to the control of cytoskeleton organization. Immunodeficiency is mainly due to ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-10-15 00:00:00
abstract::Heavy chain ferritin (H-ferritin) is a component of the iron-binding protein, ferritin. We have previously shown that H-ferritin inhibits anti-CD3-stimulated lymphocyte proliferation and that this was due to increased production of interleukin-10 (IL-10). In the present study we have shown that induction of IL-10 prod...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.9.3326
更新日期:2002-05-01 00:00:00
abstract::Erythroblastic synartesis is a rare form of acquired dyserythropoiesis, first described by Breton-Gorius et al in 1973. This syndrome is characterized by the presence of septate-like membrane junctions and "glove finger" invaginations between erythroblasts, which are very tightly linked together. This phenomenon, resp...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-12-01 00:00:00