Melanophore Migration and Survival during Zebrafish Adult Pigment Stripe Development Require the Immunoglobulin Superfamily Adhesion Molecule Igsf11

Abstract This study demonstrates that the human platelet F11 receptor (F11R) functions as an adhesion molecule, and this finding is confirmed by the structure of the protein as revealed by molecular cloning. The F11R is a 32-/35-kd protein duplex that serves as the binding site through which a stimulatory monoclonal antibody causes platelet aggregation and granule secretion. A physiological role for the F11R protein was demonstrated by its phosphorylation after the stimulation of platelets by thrombin and collagen. A pathophysiological role for the F11R was revealed by demonstrating the presence of F11R-antibodies in patients with thrombocytopenia. Adhesion of platelets through the F11R resulted in events characteristic of the action of cell adhesion molecules (CAMs). To determine the structure of this protein, we cloned the F11R cDNA from human platelets. The predicted amino acid sequence demonstrated that it is an integral membrane protein and an immunoglobulin superfamily member containing 2 extracellular C2-type domains. The structure of the F11R as a member of a CAM family of proteins and its activity in mediating adhesion confirm each another. We conclude that the F11R is a platelet-membrane protein involved in 2 distinct processes initiated on the platelet surface. The first is antibody-induced platelet aggregation and secretion that are dependent on both the FcγRII and the GPIIb/IIIa integrin and that may be involved in pathophysiological processes associated with certain thrombocytopenias. The second is an F11R-mediated platelet adhesion that is not dependent on either the FcγRII or the fibrinogen receptor and that appears to play a role in physiological processes associated with platelet adhesion and aggregation.

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Targeted gene deletion demonstrates that the cell adhesion molecule ICAM-4 is critical for erythroblastic island formation

Blood ◽

10.1182/blood-2006-03-006759 ◽

2006 ◽

Vol 108 (6) ◽

pp. 2064-2071 ◽

Cited By ~ 82

Author(s):

Gloria Lee ◽

Annie Lo ◽

Sarah A. Short ◽

Tosti J. Mankelow ◽

Frances Spring ◽

...

Keyword(s):

Adhesion Molecule ◽

Molecular Mechanisms ◽

Intercellular Adhesion Molecule ◽

Immunoglobulin Superfamily ◽

Erythroid Progenitors ◽

Island Formation ◽

Knock Out ◽

Erythroblastic Island ◽

Adhesive Interactions ◽

Knock Out Mice

AbstractErythroid progenitors differentiate in erythroblastic islands, bone marrow niches composed of erythroblasts surrounding a central macrophage. Evidence suggests that within islands adhesive interactions regulate erythropoiesis and apoptosis. We are exploring whether erythroid intercellular adhesion molecule 4 (ICAM-4), an immunoglobulin superfamily member, participates in island formation. Earlier, we identified αV integrins as ICAM-4 counterreceptors. Because macrophages express αV, ICAM-4 potentially mediates island attachments. To test this, we generated ICAM-4 knock-out mice and developed quantitative, live cell techniques for harvesting intact islands and for re-forming islands in vitro. We observed a 47% decrease in islands reconstituted from ICAM-4 null marrow compared to wild-type marrow. We also found a striking decrease in islands formed in vivo in knock-out mice. Further, peptides that block ICAM-4/αV adhesion produced a 53% to 57% decrease in reconstituted islands, strongly suggesting that ICAM-4 binding to macrophage αV functions in island integrity. Importantly, we documented that αV integrin is expressed in macrophages isolated from erythroblastic islands. Collectively, these data provide convincing evidence that ICAM-4 is critical in erythroblastic island formation via ICAM-4/αV adhesion and also demonstrate that the novel experimental strategies we developed will be valuable in exploring molecular mechanisms of erythroblastic island formation and their functional role in regulating erythropoiesis.

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Axonal cell-adhesion molecule L1 in CNS myelination

Neuron Glia Biology ◽

10.1017/s1740925x04000092 ◽

2004 ◽

Vol 1 (1) ◽

pp. 65-72 ◽

Cited By ~ 33

Author(s):

G. BARBIN ◽

M.S. AIGROT ◽

P. CHARLES ◽

A. FOUCHER ◽

M. GRUMET ◽

...

Keyword(s):

Cell Adhesion ◽

Adhesion Molecule ◽

Cell Adhesion Molecule ◽

Culture Medium ◽

Immunoglobulin Superfamily ◽

Map Kinase Pathway ◽

Cell Adhesion Molecule L1 ◽

Cns Myelination ◽

Kinase Pathway

Of the axonal signals influencing myelination, adhesion molecules expressed at the axonal surface are strong candidates to mediate interactions between myelinating cells and axons. The recognition cell-adhesion molecule L1, a member of the immunoglobulin superfamily has been shown to play important roles in neuronal migration and survival, and in PNS myelination. We have investigated the role of axonally expressed L1 in CNS myelination. In co-cultures of myelinating oligodendrocytes and neurons derived from murine brain, we demonstrate that, before myelination, L1 immunoreactivity is confined to neurites. After myelination commences, L1 expression is downregulated on myelinated axons and adjacent, but not yet myelinated, internodes. Interfering with L1 before the onset of myelination, by adding either anti-L1 antibody or L1-Fc fusion proteins to the culture medium, inhibits myelination. In addition, in purified cultures of oligodendrocytes, L1-Fc fusion protein prevents lysophosphatidic acid-induced activation of the mitogen-activated kinase (MAP)-kinase pathway. Together, our data indicate that L1 is involved in the initiation of CNS myelination, and that this effect might involve the dephosphorylation of oligodendroglial phosphoproteins.

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Adhesion Molecule ICAM-4 Participates in Erythroblastic Island Formation.

Blood ◽

10.1182/blood.v104.11.580.580 ◽

2004 ◽

Vol 104 (11) ◽

pp. 580-580

Author(s):

Gloria Lee ◽

Annie Lo ◽

Sarah Short ◽

Tosti Mankelow ◽

Stephen Parsons ◽

...

Keyword(s):

Bone Marrow ◽

Single Cell ◽

Adhesion Molecule ◽

Intracellular Signaling ◽

Targeted Mutagenesis ◽

Immunoglobulin Superfamily ◽

Mouse Bone Marrow ◽

Island Formation ◽

Erythroblastic Island ◽

Extracellular Region

Abstract Erythroblasts proliferate, differentiate and enucleate within erythroblastic islands, three dimensional structures comprised of developing erythroblasts surrounding a central macrophage. Collective evidence suggests that erythroblastic islands are highly specialized bone marrow subcompartments where adhesion events, in concert with cytokines, play critical roles in regulating erythropoiesis and apoptosis. ICAM-4, a recently characterized member of the immunoglobulin superfamily, is expressed early in erythroid differentiation. This adhesion molecule interacts with multiple integrin binding partners, including alpha4beta1 and alphaV integrins (alphaVbeta1, alphaVbeta3 and alphaVbeta5). Since erythroblasts express alpha4beta1 and ICAM-4 and macrophages exhibit alphaV, ICAM-4 is an attractive candidate for mediating erythroblast-erythroblast and erythroblast-macrophage attachments. A molecular model of ICAM-4 derived from the crystal structure of closely related ICAM-2 presents the extracellular region of ICAM-4 as two Ig-like domains comprised of A,B,C,D,E,F, and G strands. Employing targeted mutagenesis of surface-exposed amino acid residues, we earlier identified a patch or footprint that mediates adhesion to alphaV integrins comprised of three A strand residues and five G strand residues on N-terminal domain 1. To explore whether ICAM-4 attachments are active in erythroblastic islands we first developed a quantitative live cell assay for reforming islands from single cell suspensions of freshly harvested mouse bone marrow. Islands and their cellular components were identified and quantitated by three-color immunofluorescent microscopy employing fluoresceinated erythroid-specific TER119 antibody, macrophage-specific F4/80 antibody and a DNA probe. To determine the amount of variation in number of islands reformed from a single cell suspension of 1 x 105 cells, we counted islands at the beginning and conclusion of experiments on five different mice. The island numbers were very reproducible and equaled 1000 +/− 158. We then tested the effects of two synthetic peptides that we have previously shown block ICAM-4/alphaV adhesion: peptides FWV and ATSR, corresponding to sequences of the A and G strands of ICAM-4 domain 1, respectively. Both peptides caused a marked, concentration dependent decrease in the percentage of islands formed. 2mM ATSR inhibited island formation by 75% while 2mM FWV inhibited island formation by 70%. In marked contrast, a strand D control peptide had minimal to no effect on island formation. Our data strongly suggest that erythroblast ICAM-4 binding to macrophage alphaV is critical for erythroblastic island formation. We postulate that this newly identified receptor-counterreceptor interaction may be important not only for adhesive integrity of the island structure but also for initiating intracellular signaling essential for normal erythroid terminal differentiation.

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Cloning of the human platelet F11 receptor: a cell adhesion molecule member of the immunoglobulin superfamily involved in platelet aggregation

Blood ◽

10.1182/blood.v95.8.2600.008k28_2600_2609 ◽

2000 ◽

Vol 95 (8) ◽

pp. 2600-2609

Author(s):

Malgorzata B. Sobocka ◽

Tomasz Sobocki ◽

Probal Banerjee ◽

Cipora Weiss ◽

Julie I. Rushbrook ◽

...

Keyword(s):

Cell Adhesion ◽

Platelet Aggregation ◽

Membrane Protein ◽

Adhesion Molecule ◽

Platelet Adhesion ◽

Human Platelet ◽

Physiological Role ◽

Immunoglobulin Superfamily ◽

Predicted Amino Acid Sequence ◽

Platelet Surface

This study demonstrates that the human platelet F11 receptor (F11R) functions as an adhesion molecule, and this finding is confirmed by the structure of the protein as revealed by molecular cloning. The F11R is a 32-/35-kd protein duplex that serves as the binding site through which a stimulatory monoclonal antibody causes platelet aggregation and granule secretion. A physiological role for the F11R protein was demonstrated by its phosphorylation after the stimulation of platelets by thrombin and collagen. A pathophysiological role for the F11R was revealed by demonstrating the presence of F11R-antibodies in patients with thrombocytopenia. Adhesion of platelets through the F11R resulted in events characteristic of the action of cell adhesion molecules (CAMs). To determine the structure of this protein, we cloned the F11R cDNA from human platelets. The predicted amino acid sequence demonstrated that it is an integral membrane protein and an immunoglobulin superfamily member containing 2 extracellular C2-type domains. The structure of the F11R as a member of a CAM family of proteins and its activity in mediating adhesion confirm each another. We conclude that the F11R is a platelet-membrane protein involved in 2 distinct processes initiated on the platelet surface. The first is antibody-induced platelet aggregation and secretion that are dependent on both the FcγRII and the GPIIb/IIIa integrin and that may be involved in pathophysiological processes associated with certain thrombocytopenias. The second is an F11R-mediated platelet adhesion that is not dependent on either the FcγRII or the fibrinogen receptor and that appears to play a role in physiological processes associated with platelet adhesion and aggregation.

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Axon fasciculation defects and retinal dysplasias in mice lacking the immunoglobulin superfamily adhesion molecule BEN/ALCAM/SC1

Molecular and Cellular Neuroscience ◽

10.1016/j.mcn.2004.06.005 ◽

2004 ◽

Vol 27 (1) ◽

pp. 59-69 ◽

Cited By ~ 71

Author(s):

Joshua A. Weiner ◽

Sonya J. Koo ◽

Stéphane Nicolas ◽

Sandrine Fraboulet ◽

Samuel L. Pfaff ◽

...

Keyword(s):

Adhesion Molecule ◽

Immunoglobulin Superfamily

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Direct and Regulated Interaction of Integrin αEβ7 with E-Cadherin

The Journal of Cell Biology ◽

10.1083/jcb.140.1.197 ◽

1998 ◽

Vol 140 (1) ◽

pp. 197-210 ◽

Cited By ~ 150

Author(s):

Jonathan M.G. Higgins ◽

Didier A. Mandlebrot ◽

Sunil K. Shaw ◽

Gary J. Russell ◽

Elizabeth A. Murphy ◽

...

Keyword(s):

Cell Adhesion ◽

Fusion Protein ◽

Adhesion Molecule ◽

Cell Adhesion Molecule ◽

Divalent Cations ◽

Cell Receptor ◽

Intraepithelial Lymphocytes ◽

Vital Role ◽

Immunoglobulin Superfamily ◽

E Cadherin

The cadherins are a family of homophilic adhesion molecules that play a vital role in the formation of cellular junctions and in tissue morphogenesis. Members of the integrin family are also involved in cell to cell adhesion, but bind heterophilically to immunoglobulin superfamily molecules such as intracellular adhesion molecule (ICAM)–1, vascular cell adhesion molecule (VCAM)–1, or mucosal addressin cell adhesion molecule (MadCAM)–1. Recently, an interaction between epithelial (E-) cadherin and the mucosal lymphocyte integrin, αEβ7, has been proposed. Here, we demonstrate that a human E-cadherin–Fc fusion protein binds directly to soluble recombinant αEβ7, and to αEβ7 solubilized from intraepithelial T lymphocytes. Furthermore, intraepithelial lymphocytes or transfected JY′ cells expressing the αEβ7 integrin adhere strongly to purified E-cadherin–Fc coated on plastic, and the adhesion can be inhibited by antibodies to αEβ7 or E-cadherin. The binding of αEβ7 integrin to cadherins is selective since cell adhesion to P-cadherin–Fc through αEβ7 requires >100-fold more fusion protein than to E-cadherin–Fc. Although the structure of the αE-chain is unique among integrins, the avidity of αEβ7 for E-cadherin can be regulated by divalent cations or phorbol myristate acetate. Cross-linking of the T cell receptor complex on intraepithelial lymphocytes increases the avidity of αEβ7 for E-cadherin, and may provide a mechanism for the adherence and activation of lymphocytes within the epithelium in the presence of specific foreign antigen. Thus, despite its dissimilarity to known integrin ligands, the specific molecular interaction demonstrated here indicates that E-cadherin is a direct counter receptor for the αEβ7 integrin.

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Junctional adhesion molecule (JAM) binds to PAR-3

The Journal of Cell Biology ◽

10.1083/jcb.200103047 ◽

2001 ◽

Vol 154 (3) ◽

pp. 491-498 ◽

Cited By ~ 258

Author(s):

Masahiko Itoh ◽

Hiroyuki Sasaki ◽

Mikio Furuse ◽

Harunobu Ozaki ◽

Toru Kita ◽

...

Keyword(s):

Adhesion Molecule ◽

Plasma Membranes ◽

Molecular Mechanisms ◽

Spatial Relationship ◽

Immunoglobulin Superfamily ◽

Binding Assays ◽

Adhesion Sites ◽

Vitro Binding ◽

Self Association

At tight junctions (TJs), claudins with four transmembrane domains are incorporated into TJ strands. Junctional adhesion molecule (JAM), which belongs to the immunoglobulin superfamily, is also localized at TJs, but it remains unclear how JAM is integrated into TJs. Immunoreplica electron microscopy revealed that JAM showed an intimate spatial relationship with TJ strands in epithelial cells. In L fibroblasts expressing exogenous JAM, JAM was concentrated at cell–cell adhesion sites, where there were no strand-like structures, but rather characteristic membrane domains free of intramembranous particles were detected. These domains were specifically labeled with anti-JAM polyclonal antibody, suggesting that JAM forms planar aggregates through their lateral self-association. Immunofluorescence microscopy and in vitro binding assays revealed that ZO-1 directly binds to the COOH termini of claudins and JAM at its PDZ1 and PDZ3 domains, respectively. Furthermore, another PDZ-containing polarity-related protein, PAR-3, was directly bound to the COOH terminus of JAM, but not to that of claudins. These findings led to a molecular architectural model for TJs: small aggregates of JAM are tethered to claudin-based strands through ZO-1, and these JAM aggregates recruit PAR-3 to TJs. We also discuss the importance of this model from the perspective of the general molecular mechanisms behind the recruitment of PAR proteins to plasma membranes.

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