Integrins alpha v beta 3 and alpha v beta 5 contribute to cell attachment to vitronectin but differentially distribute on the cell surface.

Wayner, Elizabeth A.; Orlando, Robert A.; Cheresh, David A.

doi:10.1083/jcb.113.4.919

Cited by 324 publications

(197 citation statements)

References 44 publications

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“…Indeed, inclusion of the function-blocking anti-␣ v ␤ 5 integrin antibody P1F6 in adhesion experiments completely inhibited CHO-B2 adhesion to vitronectin and partially blocked adhesion to Ang-2 (data not shown). Initial studies of ␣ v ␤ 5 -mediated cell adhesion to vitronectin established that ␣ v ␤ 5 does not localize to focal contacts or associate with the actin cytoskeleton (34). Subsequent studies found that activation of protein kinase C indirectly via epidermal growth factor stimulation or directly with phorbol esters promoted ␣ v ␤ 5 -mediated cell spreading, focal contact formation, and migration on vitronectin (35,36).…”

Section: Discussionmentioning

confidence: 99%

Direct Cell Adhesion to the Angiopoietins Mediated by Integrins

Carlson¹,

Feng²,

Maisonpierre³

et al. 2001

Journal of Biological Chemistry

239

210

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It is therefore possible that Ang-1 regulates endothelial cell adhesion. In this study we asked whether Ang-1 might act as a direct substrate for cell adhesion. Human umbilical vein endothelial cells (HUVECs) plated for a brief period on different substrates were found to adhere and spread well on Ang-1. Similar results were seen on angiopoietin-2 (Ang-2)-coated surfaces, although cells did not spread well on Ang-2. Ang-1, but not Ang-2, supported HUVEC migration, and this was independent of growth factor activity. When the same experiments were done with fibroblasts that either lacked, or stably expressed, Tie2, results similar to those with HUVECs were seen, suggesting that adhesion to the angiopoietins was independent of Tie2 and not limited to endothelial cells. Interestingly, when integrin-blocking agents were included in these assays, adhesion to either angiopoietin was significantly reduced. Moreover, Chinese hamster ovary-B2 cells lacking the ␣ 5 integrin subunit did not adhere to Ang-1, but they did adhere to Ang-2. Stable expression of the human ␣ 5 integrin subunit in these cells rescued adhesion to Ang-1 and promoted an increase in adhesion to Ang-2. We also found that Ang-1 and Ang-2 bind rather selectively to vitronectin. These results suggest that, beyond their role in modulating Tie2 signaling, Ang-1 and Ang-2 can directly support cell adhesion mediated by integrins.Angiogenesis, the de novo sprouting and remodeling of capillaries from preexisting blood vessels, is a critical process during both vertebrate development and adult life (4). This process can be divided into several distinct, often overlapping, phases. In general, angiogenesis initiates with vasodilation and increases in endothelial permeability. Subsequently, endothelial cells begin to proliferate and migrate toward the angiogenic stimulus. During the final maturation stages, the endothelial cells acquire a more differentiated state marked by lumen formation and production and assembly of a complex basement membrane. Finally, periendothelial cells are recruited into the area thereby providing further support for the new vessel. A balance between stimulatory and inhibitory signals controls each step during angiogenesis. Such signals can arrive in the form of growth factors, cytokines, and extracellular matrix (ECM) 1 proteins, to name a few. These extracellular cues are then transduced to the cytoplasm by various different classes of cell surface receptors, with the most common being members of either the receptor tyrosine kinase or integrin superfamilies (5).The angiopoietins, along with their cell surface receptor tyrosine kinase, Tie2, comprise one of the most widely studied families of angiogenic factors. Unlike other well known angiogenic factors, the angiopoietins are not mitogenic for endothelial cells. Thus, their biological function is not well understood. The angiopoietin family members contain an N-terminal coiled-coil domain as well as a C-terminal fibrinogen-like domain that shares a high degree of homology to the analogo...

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Section: Discussionmentioning

confidence: 99%

Direct Cell Adhesion to the Angiopoietins Mediated by Integrins

Carlson¹,

Feng²,

Maisonpierre³

et al. 2001

Journal of Biological Chemistry

239

210

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“…Another suggestion is that they are a normal adhesion structure found in highly motile cells (Nermut et al, 199 1). The results of studies on carcinoma cell adhesion and spreading have suggested that integrins in point contacts are unable to interact with the cytoskeleton (Wayner et al, 1991). Recent antibody blocking experiments performed with astrocytes that express both point contacts and focal contacts demonstrate that point contacts can be functional sites of adhesion (Tawil et al, 1993).…”

Section: Point Contactsmentioning

confidence: 99%

Characterization of neural cell adhesion sites: point contacts are the sites of interaction between integrins and the cytoskeleton in PC12 cells

1994

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As developing or regenerating neurons grow, their axons seek cues in the extracellular matrix that are recognized by integrin receptors. To understand the regulation and structure of neural integrin complexes, we have examined the association of two functionally important integrins, alpha 1 beta 1 and alpha 3 beta 1, within PC12 cells. Detergent-resistant cytoskeletal ghosts were prepared from PC12 cells and examined by immunoblotting. In cells maintained in suspension the alpha 1, alpha 3, and beta 1 integrin subunits were solubilized by Triton X-100 detergent. In contrast, when cells were grown on collagen or laminin about 50% of the alpha 1 and beta 1 subunits were retained with the cytoskeleton, but alpha 3 remained soluble. Confocal immunofluorescence microscopy of whole cells demonstrated that all three integrin subunits were expressed in a punctate pattern on the cell surface in point contacts. Point contacts were also found to be the predominant adhesion structure of dorsal root ganglion neurons. After detergent extraction of PC12 cells, the point contacts remained only at the cell-substrate interface. Vinculin, which is found consistently in focal contacts on non-neural cells, showed only a partial colocalization with the point contacts, being expressed mainly at the tips of filopodia and the periphery of cell bodies. Talin showed no obvious codistribution with beta 1 integrin immunoreactivity in point contacts. Immunoreactivity to p125FAK was not detected in PC12 cells, although astrocytes, which have both focal contacts and point contacts have p125FAK only at focal contacts. These observations, together with previous data (Turner et al., 1989; Tawil et al., 1993), suggest that point contacts are functional adhesion sites and are structurally distinct from focal contacts found in non-neuronal cells.

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“…For example, the fibronectin receptor, «5ß,, concentrates in focal contacts in cells spread on a substrate of fibronectin ; the vitronectin receptor, aß3, is in focal contacts in cells spread on vitronectin ; and on a collagen substrate, the collagen receptor, a2ß,, is in focal contacts (Singer et al, 1988;Dejana et al ., 1988;Fath et al ., 1989;Carter et al, 1990). However, it is puzzling that the vitronectin receptor, «vß5 , does not localize to focal contacts (Wayner et al, 1991), even though it contains sequence motifs previously demonstrated to be important in receptor localization to these adhesion sites (McLean et al ., 1990;Ramaswamy and Hemler, 1990;Marcantonio et al, 1990) . Thus, the molecular mechanisms ofthe regulation ofintegrin receptor distribution and the specific contributions of the various aspects of receptor function to this process are still unknown .…”

mentioning

confidence: 99%

Regulation of fibronectin receptor distribution [published erratum appears in J Cell Biol 1992 Jul;118(2):491]

LaFlamme

Akiyama

Yamada

1992

The Journal of Cell Biology

266

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Abstract. To determine the role of each intracellular domain of the fibronectin receptor in receptor distribution, chimeric receptors were constructed containing the human interleukin-2 receptor (gp55 subunit) as the extracellular and transmembrane domains, in combination with either the a5 or ß, intracellular domain of the fibronectin receptor as the cytoplasmic domain . These chimeric receptors were transiently expressed in normal fibroblasts, and their localization on the cell surface was determined by immunofluorescence using antibodies to the human interleukin-2 receptor. The a5 chimera was expressed diffusely on the plasma membrane . The 01 chimera, however, colocalized with the endogenous fibronectin receptor at focal contacts of cells spread on fibronectin . On cells spread in the presence of serum, the 01 chimera colocalized both with the fibronectin receptor at sites of extracellular fibronectin fibrils and with the vitronectin receptor at focal contacts. The 01 intracellular domain alone, therefore, contains sufficient information to target the chimeric receptor to regions of the cell where ligandoccupied integrin receptors are concentrated. The find-T HE integrins, a family of transmembrane heterodimeric receptors consisting of a and ß subunits, play a central role in cell adhesion and migration . These processes are important in development, wound healing, metastasis, and other biological events. Integrins function in both cell-cell and cell-substratum adhesion . Integrin heterodimers can be classified into subfamilies based on the different ß subunits. Different combinations of a and ß subunits give rise to receptors with different ligand specificities, including receptors for fibronectin, vitronectin, collagen, and laminin. Although some integrins are cell-type specific, most function in many cell types, and most cell types express a variety ofintegrin receptors, allowing them to interact with many extracellular matrix components (recent reviews include Akiyama et al

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Integrins alpha v beta 3 and alpha v beta 5 contribute to cell attachment to vitronectin but differentially distribute on the cell surface.

Cited by 324 publications

References 44 publications

Direct Cell Adhesion to the Angiopoietins Mediated by Integrins

Direct Cell Adhesion to the Angiopoietins Mediated by Integrins

Characterization of neural cell adhesion sites: point contacts are the sites of interaction between integrins and the cytoskeleton in PC12 cells

Regulation of fibronectin receptor distribution [published erratum appears in J Cell Biol 1992 Jul;118(2):491]

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