Dogic D, Rousselle P, Aumailley MCell adhesion to laminin 1 or 5 induces isoform-specific clustering of integrins and other focal adhesion components. J Cell Sci 111:793-802 (original) (raw)
Related papers
Journal of cell science, 2000
Laminin-10/11, the laminin isoforms containing the alpha 5 chain, are major components of basement membranes of many fetal and adult tissues. Laminin-10/11 purified from the conditioned medium of human lung carcinoma cells were potent in mediating adhesion of the carcinoma cells in an integrin alpha 3 beta 1-dependent manner. To further define the type(s) of integrins involved in cell adhesion to laminin-10/11, we examined the effects of a panel of function-blocking anti-integrin antibodies on the adhesion of different cell types to laminin-10/11. Although anti-integrin beta 1 antibody inhibited the adhesion of all cell types tested, anti-alpha 3 antibody inhibited the adhesion of carcinoma and glioma cells but not fibroblastic cells. Adhesion of fibroblastic cells was inhibited, however, by a combination of anti-alpha 3 and anti-alpha 6 antibodies, suggesting that both alpha 3 beta 1 and alpha 6 beta 1 integrins function as laminin-10/11 receptors in these cells. To explore this po...
A Novel Recognition Site on Laminin for the α3β1 Integrin
Experimental Cell Research, 1996
hesion, migration, protease secretion, and angiogenesis Synthetic peptide GD-2 is a sequence of amino acids . Proteolytic fragments of laminin and synthetic derived from the carboxy-terminal long arm of the A peptides corresponding to amino acid sequences within chain of laminin. Previous studies have shown that laminin have been utilized to identify specific domains peptide GD-2 promotes the adhesion of human squaof laminin that mediate specific activities involved in mous cell carcinoma (SCC) cells as well as a variety of the metastatic process . At present, three synthetic other cell lines. In this study, we attempted to identify peptides derived from laminin, YIGSR, PDSGR, and the receptor that SCC cells use to adhere to peptide SIKVAV, have been reported to alter metastasis of tu-GD-2. Monoclonal antibodies (mAbs) against a human mor cells in mice [4 -6]. Another laminin peptide, GD-SCC cell line were generated. One of these mAbs, ASC-2, has been shown to promote the adhesion of a variety 1, bound to the surface of SCC cells as determined by of cell types, including human squamous cell carcinoma flow cytometry. This mAb inhibited SCC cell adhesion (SCC) cell lines and HT-1080 human fibrosarcoma cells to peptide GD-2 and laminin, but not fibronectin or [7,. In addition, peptide GD-2 has been shown to type IV collagen, suggesting that mAb ASC-1 binds to promote the outgrowth of neurites from chick spinal the SCC receptor for the peptide GD-2 sequence of lamcord and dorsal root ganglia neurons . The identifiinin. MAb ASC-1 immunoprecipitated a complex comcation of sites on laminin that promote cell adhesion posed of two components of 135 and 116 kDa. Immuand the identification of receptors on cell surfaces that noadsorption of ASC-1-binding material from the SCC bind laminin are important in understanding the role cell extract by incubation with mAb ASC-1 resulted of laminin in cell adhesion and the metastatic process in the removal of the a3b1 integrin from the extract. of tumor cells. Immunohistochemical staining of tissue from a normal Integrins are a family of transmembrane heterodihuman tongue and from a patient with SCC of the meric glycoproteins composed of a and b subunits that tongue revealed that mAb ASC-1 stained the surface of function in cell -matrix and cell-cell adhesion [9 -11].
Experimental Cell Research, 2004
The presence of many laminin receptors of the h1 integrin family on most cells makes it difficult to define the biological functions of other major laminin receptors such as integrin a6h4 and dystroglycan. We therefore tested the binding of a h1 integrin-null cell line GD25 to four different laminin variants. The cells were shown to produce dystroglycan, which based on affinity chromatography bound to laminin-1, -2/4, and -10/11, but not to laminin-5. The cells also expressed the integrin a6Ah4A variant. GD25 h1 integrin-null cells are known to bind poorly to laminin-1, but we demonstrate here that these cells bind avidly to laminin-2/4, -5, and -10/11. The initial binding at 20 min to each of these laminins could be inhibited by an integrin a6 antibody, but not by a dystroglycan antibody. Hence, integrin a6Ah4A of GD25 cells was identified as a major receptor for initial GD25 cell adhesion to three out of four tested laminin isoforms. Remarkably, cell adhesion to laminin-5 failed to promote cell spreading, proliferation, and extracellular signal-regulated kinase (ERK) activation, whereas all these responses occurred in response to adhesion to laminin-2/4 or -10/11. The data establish GD25 cells as useful tools to define the role integrin a6Ah4A and suggest that laminin isoforms have distinctly different capacities to promote cell adhesion and signaling via integrin a6Ah4A. D
Integrins as receptors for laminins
Microscopy Research and Technique, 2000
Laminins are a family of trimeric glycoproteins present in the extracellular matrix and the major constituents of basement membranes. Integrins are ␣ transmembrane receptors that play critical roles in both cell-matrix and cell-cell adhesion. Several members of the integrin family, including ␣11, ␣21, ␣31, ␣61 , ␣71 and ␣64 heterodimers serve as laminin receptors on a variety of cell types. This review summarizes recent advances in understanding the involvement of individual integrins in cell interactions with laminins and the roles of laminin-binding integrins in adhesion-mediated events in vertebrates, including embryonic development, cell migration and tumor cell invasiveness, cell proliferation and differentiation, as well as basement membrane assembly. We discuss the regulation of integrin function via alternative splicing of cytoplasmic domains of ␣ and  subunits of the integrin receptors for laminins and present examples of functional collaboration between laminin-binding integrins and non-integrin laminin receptors. Advances in our understanding of the laminin-binding integrins continue to demonstrate the essential roles these receptors play in maintaining cell polarity and tissue architecture. Microsc.
2004
The presence of many laminin receptors of the h1 integrin family on most cells makes it difficult to define the biological functions of other major laminin receptors such as integrin a6h4 and dystroglycan. We therefore tested the binding of a h1 integrin-null cell line GD25 to four different laminin variants. The cells were shown to produce dystroglycan, which based on affinity chromatography bound to laminin-1,-2/4, and-10/11, but not to laminin-5. The cells also expressed the integrin a6Ah4A variant. GD25 h1 integrin-null cells are known to bind poorly to laminin-1, but we demonstrate here that these cells bind avidly to laminin-2/4,-5, and-10/11. The initial binding at 20 min to each of these laminins could be inhibited by an integrin a6 antibody, but not by a dystroglycan antibody. Hence, integrin a6Ah4A of GD25 cells was identified as a major receptor for initial GD25 cell adhesion to three out of four tested laminin isoforms. Remarkably, cell adhesion to laminin-5 failed to promote cell spreading, proliferation, and extracellular signal-regulated kinase (ERK) activation, whereas all these responses occurred in response to adhesion to laminin-2/4 or-10/11. The data establish GD25 cells as useful tools to define the role integrin a6Ah4A and suggest that laminin isoforms have distinctly different capacities to promote cell adhesion and signaling via integrin a6Ah4A.
Integrin alpha 6 beta 4 mediates dynamic interactions with laminin
Journal of cell science, 1994
We present here a novel form of dynamic adhesion in which both the integrin receptor and the ligand supporting dynamic adhesion have been identified. Laminar flow assays showed that laminin supported attachment of alpha 6 beta 4-positive cells in the presence of fluid shear stress (tau < or = 2 dyn/cm2), indicating that these cells adhered to laminin within a fraction of a second. Further increases in flow rate (3.5 dyn/cm2 < or = tau < or = 100 dyn/cm2) initiated rolling of attached cells in the direction of flow, suggesting that rapidly formed adhesion is reversible and repeatable. Laminin fragment E8, which interacts with alpha 6 integrins, supported dynamic attachment and rolling but extracellular matrix glycoprotein fibronectin did not. In cell lines that express alpha 6 beta 4 but not alpha 6 beta 1 an anti-alpha 6 monoclonal antibody inhibited attachment to laminin in the presence of flow and following 5 minutes of static incubation. Infusion of this antibody onto ce...
The Journal of Cell Biology
The involvement of integrins in mediating interaction of cells to well-characterized proteolytic fragments (P1, E3, and E8) of laminin was assessed by antibody blocking studies. Cell adhesion to fragment P1 was affected by mAbs against the integrin/51 and /53 subunits and furthermore could be prevented completely by a synthetic peptide containing the Arg-Gly-Asp sequence. Because the 153 antibody-sensitive cell lines expressed the vitronectin receptor (otv/53) at high levels, the involvement of this receptor in cell adhesion to P1 is strongly suggested. Integrin-mediated cell adhesion to E3 is of low affinity and was inhibited by antibodies against the integrin/51 subunit. In contrast, adhesion of some cell types to E3 was not or only partially sensitive to inhibition by anti-integrin subunit antibodies. Cell adhesion to E8 was blocked completed by integrin ct6 or/51 antibodies. The t~6-specific antibody did not inhibit cell adhesion to E3 or P1. Furthermore, the antibody only blocked adhesion to Cell lines used included the human ovarian carcinoma OVCAR-4, the human normal mammary HBL-100, the human mammary tumor T47D, and the human melanoma A375, and the mouse mammary tumor cell lines 1. Abbreviations used in this paper: EHS, Englebreth-Holm-Swarm tumor.
The Laminin α2-Chain Short Arm Mediates Cell Adhesion through Both the α1β1 and α2β1 Integrins
Journal of Biological Chemistry, 1997
Laminin-2, a heterotrimer composed of ␣2, 1, and ␥1 subunits, is the primary laminin isoform found in muscle and peripheral nerve and is essential for the development and stability of basement membranes in these tissues. Expression of a domain VI-truncated laminin ␣2-chain results in muscle degeneration and peripheral nerve dysmyelination in the dy 2J dystrophic mouse. We have expressed amino-terminal domains VI through IVb of the laminin ␣2-chain, as well as its laminin-1 ␣1-chain counterpart, to identify candidate cell-interactive functions of this critical region. Using integrin-specific antibodies, recognition sites for the ␣11 and ␣21 integrins were identified in the short arms of both laminin ␣1and ␣2-chain isoforms. Comparisons with a -␣ chimeric short arm protein possessing 1-chain domain VI further localized these activities to ␣-chain domain VI. In addition, we found that the laminin ␣2-chain short arm supported neurite outgrowth independent of other laminin-2 subunits. A heparin/heparan sulfate binding activity was also localized to this region of the laminin ␣2 subunit. These data provide the first evidence that domain VI of the laminin ␣2-chain mediates interactions with cell surface receptors and suggest that these integrin and heparin binding sites, alone or in concert, may play an important role in muscle and peripheral nerve function.
Journal of Biological Chemistry, 2001
Laminins are a family of extracellular matrix glycoproteins involved in cell adhesion and migration. A major obstacle to understanding their structure-function relationships is the lack of small laminin domains capable of replicating integrin-binding, cell-adhesive, and migratory functions of the intact molecule. Here, we show that the recombinant LG3 (rLG3) module (26 kDa) of laminin-5 (Ln-5) ␣ 3 chain replicated key Ln-5 activities. rLG3 but not rLG1 or rLG2 supported cell adhesion and migration of at least two distinct cell lines, in an integrin ␣ 3  1-dependent manner. Cell adhesion to rLG3 was regulated by divalent cations and accompanied by cell spreading and tyrosine phosphorylation of FAK focal adhesion kinase. The integrin binding activity of rLG3 was confirmed by rLG3 affinity chromatography of detergent cell lysates, which resulted in specific purification of integrin ␣ 3  1. To our knowledge, this is the first report directly demonstrating that a recombinant laminin LG module is an active domain capable of supporting integrin-dependent cell adhesion and migration.