skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Tetraspanins CD81 and CD82 Facilitate α4β1-Mediated Adhesion of Human Erythroblasts to Vascular Cell Adhesion Molecule-1

Journal Article · · PLoS ONE
 [1];  [1];  [1];  [2];  [1];  [3];  [1]
  1. Bristol Institute for Transfusion Sciences, Bristol (United Kingdom)
  2. Bristol University (United Kingdom)
  3. Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
+ Show Author Affiliations

The proliferation and terminal differentiation of erythroid progenitors occurs in human bone marrow within erythroblastic islands, specialised structures consisting of a central macrophage surrounded by developing erythroid cells. Many cell-cell and cell-matrix adhesive interactions maintain and regulate the co-ordinated daily production of reticulocytes. Erythroid cells express only one integrin, α4β1, throughout differentiation, and its interactions with both macrophage Vascular Cell Adhesion Molecule-1 and with extracellular matrix fibronectin are critical for erythropoiesis. We observed that proerythroblasts expressed a broad tetraspanin phenotype, and investigated whether any tetraspanin could modulate integrin function. A specific association between α4βb1 and CD81, CD82 and CD151 was demonstrated by confocal microscopy and co-immune precipitation. We observed that antibodies to CD81 and CD82 augmented adhesion of proerythroblasts to Vascular Cell Adhesion Molecule-1 but not to the fibronectin spliceoforms FnIII12-IIICS-15 and FnIII12–15. In contrast, different anti-CD151 antibodies augmented or inhibited adhesion of proerythroblasts to Vascular Cell Adhesion Molecule-1 and the fibronectin spliceoform FnIII12-IIICS-15 but not to FnIII12–15. These results strongly suggest that tetraspanins have a functional role in terminal erythropoiesis by modulating interactions of erythroblast α4β1 with both macrophages and extracellular matrix.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institute for Health Research; Department of Health (England); Biological and Biotechnology Research Council; National Institutes of Health (NIH)
Grant/Contract Number:
AC02-05CH11231; BB/7007256; DK32094
OSTI ID:
1627607
Journal Information:
PLoS ONE, Vol. 8, Issue 5; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

References (66)

Expression of a divalent cation-dependent erythroblast adhesion receptor by stromal macrophages from murine bone marrow journal May 1991
Molecular Identification and Functional Characterization of a Novel Protein That Mediates the Attachment of Erythroblasts to Macrophages journal October 1998
Expression and Function of Integrins on Hematopoietic Progenitor Cells journal January 1997
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 journal August 1970
Tetraspanin-enriched microdomains: a functional unit in cell plasma membranes journal September 2009
Stem cells unscramble yolk sac hematopoiesis journal August 2009
Adult murine hematopoiesis can proceed without β1 and β7 integrins journal September 2006
Correlation of in situ mechanosensitive responses of the Moraxella catarrhalis adhesin UspA1 with fibronectin and receptor CEACAM1 binding journal August 2011
Complexes of tetraspanins with integrins: more than meets the eye journal December 2001
Selective tetraspan–integrin complexes (CD81/α4β1, CD151/α3β1, CD151/α6β1) under conditions disrupting tetraspan interactions journal May 1999
α4β1Integrin-dependent Cell Adhesion Is Regulated by a Low Affinity Receptor Pool That Is Conformationally Responsive to Ligand journal December 1995
Multiple activation states of VLA-4. Mechanistic differences between adhesion to CS1/fibronectin and to vascular cell adhesion molecule-1. journal January 1993
Proteomic Analysis of Integrin-Associated Complexes Identifies RCC2 as a Dual Regulator of Rac1 and Arf6 journal September 2009
The Expression of Human Blood Group Antigens During Erythropoiesis in a Cell Culture System journal June 1999
Loss of attachment to fibronectin with terminal human erythroid differentiation journal February 1990
Isolation and characterization of resident stromal macrophages and hematopoietic cell clusters from mouse bone marrow. journal September 1985
A critical role of VLA-4 in erythropoiesis in vivo journal March 1996
α4β1 integrin and erythropoietin mediate temporally distinct steps in erythropoiesis: integrins in red cell development journal June 2007
Identification of a novel recognition sequence for the integrin alpha 4 beta 1 in the COOH-terminal heparin-binding domain of fibronectin. journal December 1991
Very late activation antigen 4-vascular cell adhesion molecule 1 interaction is involved in the formation of erythroblastic islands. journal January 1995
Combinatorial and distinct roles of α5 and α4 integrins in stress erythropoiesis in mice journal January 2011
Exosomes in erythropoiesis journal September 2010
Crystal structure of a heparin-and integrin-binding segment of human fibronectin journal March 1999
The ins and outs of human reticulocyte maturation journal July 2012
Deletion of α4 Integrins from Adult Hematopoietic Cells Reveals Roles in Homeostasis, Regeneration, and Homing journal December 2003
The macrophage CD163 surface glycoprotein is an erythroblast adhesion receptor journal June 2007
The association of erythroblasts with macrophages promotes erythroid proliferation and maturation: a 30-kD heparin-binding protein is involved in this contact journal November 1994
Engaging CD19 or target of an antiproliferative antibody 1 on human B lymphocytes induces binding of B cells to the interfollicular stroma of human tonsils via integrin alpha 4/beta 1 and fibronectin. journal November 1995
Adherence to macrophages in erythroblastic islands enhances erythroblast proliferation and increases erythrocyte production by a different mechanism than erythropoietin journal February 2008
Expression of integrins in human bone marrow journal November 1990
Role of β1-integrins and their associated tetraspanin molecules in fibronectin-enhanced megakaryopoiesis journal October 2004
Tetraspanins journal August 2001
Maturing reticulocytes internalize plasma membrane in glycophorin A–containing vesicles that fuse with autophagosomes before exocytosis journal June 2012
Role of Transmembrane 4 Superfamily (Tm4sf) Proteins Cd9 and Cd81 in Muscle Cell Fusion and Myotube Maintenance journal August 1999
Tetraspanins and Intercellular Interactions journal June 2001
Coexpression of two fibronectin receptors, VLA-4 and VLA-5, by immature human erythroblastic precursor cells. journal January 1991
A CD9, alphaIIbbeta3, integrin-associated protein, and GPIb/V/IX complex on the surface of human platelets is influenced by alphaIIbbeta3 conformational states journal July 1999
A functional genetic screen reveals new regulators of β1-integrin activity journal February 2012
Identification of Fibronectin IIICS Variants in Human Bone Marrow Stroma journal January 1999
The complexity of tetraspanins journal March 2011
Lateral organization of membrane proteins: tetraspanins spin their web journal May 2009
Identification of critical amino-acid residues on the erythroid intercellular adhesion molecule-4 (ICAM-4) mediating adhesion to αV integrins journal February 2004
Fibronectin at a glance journal October 2002
Impaired migration but not differentiation of haematopoietic stem cells in the absence of β1 integrins journal March 1996
Loss of attachment to fibronectin with terminal human erythroid differentiation journal February 1990
CD151, the first member of the tetraspanin (TM4) superfamily detected on erythrocytes, is essential for the correct assembly of human basement membranes in kidney and skin journal October 2004
Roles for integrin very late activation antigen-4 in stroma-dependent erythropoiesis journal May 1994
SWAP-70 regulates erythropoiesis by controlling  4 integrin journal August 2011
β1 Integrin Is Not Essential for Hematopoiesis but Is Necessary for the T Cell-Dependent IgM Antibody Response journal March 2002
Targeted gene deletion demonstrates that the cell adhesion molecule ICAM-4 is critical for erythroblastic island formation journal September 2006
α4 Integrins Regulate the Proliferation/Differentiation Balance of Multilineage Hematopoietic Progenitors In Vivo journal November 1999
Metabolic Activation-related CD147-CD98 Complex journal August 2005
Three-dimensional model of bone marrow journal April 1978
Erythroblastic islands: niches for erythropoiesis journal August 2008
The CD81 Tetraspanin Facilitates Instantaneous Leukocyte VLA-4 Adhesion Strengthening to Vascular Cell Adhesion Molecule 1 (VCAM-1) under Shear Flow journal December 2003
Expression of RHD and RHCE gene products using retroviral transduction of K562 cells establishes the molecular basis of Rh blood group antigens journal April 1996
Characterization of Mice Lacking the Tetraspanin Superfamily Member CD151 journal July 2004
Integrin expression profiles during erythroid differentiation journal April 1992
Molecular Identification and Functional Characterization of a Novel Protein That Mediates the Attachment of Erythroblasts to Macrophages journal October 1998
Transmembrane 4 superfamily protein CD151 (PETA-3) associates with β1 and αIIbβ3 integrins in haemopoietic cell lines and modulates cell–cell adhesion journal February 1999
Tetraspanin functions and associated microdomains journal October 2005
Differentiation of primitive human multipotent hematopoietic progenitors into single lineage clonogenic progenitors is accompanied by alterations in their interaction with fibronectin. journal September 1991
A common bipotent progenitor generates the erythroid and megakaryocyte lineages in embryonic stem cell–derived primitive hematopoiesis journal August 2009
Transmembrane-4 superfamily proteins CD81 (TAPA-1), CD82, CD63, and CD53 specifically associated with integrin alpha 4 beta 1 (CD49d/CD29). journal September 1996
CD9-regulated adhesion. Anti-CD9 monoclonal antibody induce pre-B cell adhesion to bone marrow fibroblasts through de novo recognition of fibronectin. journal March 1994
Analysis of Ligand-Induced and Ligand-Attenuated Epitopes on the Leukocyte Integrin α4β1: VCAM-1, Mucosal Addressin Cell Adhesion Molecule-1, and Fibronectin Induce Distinct Conformational Changes journal May 1998

Cited By (6)

The Activation and Signaling Mechanisms of GPR56/ADGRG1 in Melanoma Cell journal August 2018
Beyond the Matrix: The Many Non-ECM Ligands for Integrins journal February 2018
Tspan8 and Tspan8/CD151 knockout mice unravel the contribution of tumor and host exosomes to tumor progression journal December 2018
Macrophage heterogeneity in tissues: phenotypic diversity and functions journal October 2014
Cellular dynamics of mammalian red blood cell production in the erythroblastic island niche journal August 2019
HIV-1 Nef and Vpu Are Functionally Redundant Broad-Spectrum Modulators of Cell Surface Receptors, Including Tetraspanins journal December 2014

Similar Records

The peptide mimicking small extracellular loop domain of CD82 inhibits tumor cell migration, adhesion and induces apoptosis by inhibiting integrin mediated signaling
Journal Article · Sat Sep 15 00:00:00 EDT 2018 · Biochemical and Biophysical Research Communications · OSTI ID:1627607
+2 more
Targeted Gene Deletion Demonstrates that Cell Adhesion MoleculeICAM-4 is Critical for Erythroblastic Island Formation
Journal Article · Wed Feb 15 00:00:00 EST 2006 · Blood · OSTI ID:1627607
+6 more
Novel secreted isoform of adhesion molecule ICAM-4: Potential regulator of membrane-associated ICAM-4 interactions
Journal Article · Tue Feb 18 00:00:00 EST 2003 · Blood · OSTI ID:1627607
+6 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
erythroblasts
integrins
macrophages
cell adhesion
cell binding
erythropoiesis
cloning
reticulocytes