Collagen-platelet interactions: recognition and signalling

Farndale, Richard W.; Siljander, Pia; Onley, David J.; Sundaresan, Pavithra; Knight, Christopher G.; Barnes, Michael J.

doi:10.1042/bss0700081

Cited by 43 publications

(33 citation statements)

References 48 publications

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“…Here we show that L, and to a lesser extent M and A, may substitute for F in this context, but the efficacy of the binding depends on the activation state of the integrin. GAOGER has previously been proposed, but not proven, to mediate ␣ 2 ␤ 1 -dependent binding of collagen III, which does not contain GFOGER (25), while GMOGER and GLSGER sequences identified here are completely novel. The final hydrophobic amino acid-containing sequences, GIOGER, which occurs in collagens types I (chicken, frog) and III (chicken), and GVOGER, which occurs in collagens types VIII and X (human) would also be predicted to be a higher affinity integrin binding sequences as isoleucine and valine also have a large non-polar side chains.…”

Section: Discussionmentioning

confidence: 81%

“…Three conserved loci for GFOGER and GLOGER in collagen types I, II, and XI, started at residues 127, 502, and 550 in the alignment. When other sequences occur in these loci, they are usually GMOGER or GAOGER, a previously proposed recognition sequence (25). Because the C-terminal GASGER, at residue 811, occupied a less conserved site and was shown to be of poor affinity at best (16), we also identified another Cterminal GXXGER locus nearby at 787, which contains several GXXGER sequences each having a polar rather than a hydrophobic residue within the first triplet.…”

Section: Resultsmentioning

confidence: 95%

“…Competition experiments established an affinity series for the recognition motifs: GFOGER Ͼ GLOGER Ͼ GLS-GER Ͼ GMOGER Ͼ GAOGER Ϸ GASGER Ϸ GQRGER. The cellular context was found to be crucial in determining the binding to these sequences, since, in contrast to adhesion of ␣ 2 ␤ 1 -containing HT1080 cells (a constitutively adherent cell line), ␣ 2 ␤ 1 -mediated platelet adhesion was poor to GER sequences other than GFOGER unless the peptide also contained GPVI recognition motifs (GPO n ) (25,26), or the platelets were otherwise activated (27) in line with their hemostatic surveillance function. This concept was confirmed by non-selective binding of active ␣ 2 I mutants to all sequences.…”

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confidence: 99%

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Integrin Activation State Determines Selectivity for Novel Recognition Sites in Fibrillar Collagens

Siljander¹,

Hamaia²,

Peachey³

et al. 2004

Journal of Biological Chemistry

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164

188

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Only three recognition motifs, GFOGER, GLOGER, and GASGER, all present in type I collagen, have been identified to date for collagen-binding integrins, such as ␣ 2 ␤ 1 . Sequence alignment was used to investigate the occurrence of related motifs in other human fibrillar collagens, and located a conserved array of novel GER motifs within their triple helical domains. We compared the integrin binding properties of synthetic triple helical peptides containing examples of such sequences (GLSGER, GMOGER, GAOGER, and GQRGER) or the previously identified motifs. Recombinant inserted (I) domains of integrin subunits ␣ 1 , ␣ 2 , and ␣ 11 bound poorly to all motifs other than GFOGER and GLOGER. Similarly, ␣ 2 ␤ 1 -containing resting platelets adhered well only to GFOGER and GLOGER, while ADP-activated platelets, HT1080 cells and two active ␣ 2 I domain mutants (E318W, locked open) bound all motifs well, indicating that affinity modulation determines the sequence selectivity of integrins. GxO/SGER peptides inhibited platelet adhesion to collagen monomers with order of potency F > L > M > A. These results establish GFOGER as a high affinity sequence, which can interact with the ␣ 2 I domain in the absence of activation and suggest that integrin reactivity of collagens may be predicted from their GER content.Collagen, the most abundant structural protein of the vertebrate organism, currently has 27 reported family members (1). As either a mechanical support or as a bioactive surface, collagen plays a crucial role in processes as diverse as morphogenesis, wound repair, inflammation, tumor metastasis, hemostasis, and thrombosis. The tensile strength of the fibrillar collagens, types I-III, V, XI, and XXVII, is crucial to the function of connective tissues including the blood vessel wall. The non-fibrillar collagens, such as types IV and VI, provide a flexible support for endothelial and epithelial cell attachment and development. Integrins, heterodimeric adhesion molecules, form an important subgroup of receptors, which mediate interaction between collagen and cells. Four ␣-subunits, ␣ 1 , ␣ 2 , ␣ 10 , and ␣ 11 , which associate non-covalently with ␤ 1 , constitute the native collagen-binding integrin family (2).Integrin ␣ 2 ␤ 1 is a well characterized and widespread receptor for collagen, laminin, and other non-matrix ligands among nucleated cells including epithelial and endothelial cells, smooth muscle cells, fibroblasts, leukocytes, and mast cells (3, 4), mediating a wide range of cellular activities. ␣ 2 ␤ 1 is the only collagen binding integrin in platelets, and is crucial for deposition on collagens exposed in damaged arterial walls (5, 6). Accordingly, the expression levels of ␣ 2 ␤ 1 have been associated with myocardial infarction and stroke (7). Recently, knockout studies suggested that the platelet activatory collagen receptor glycoprotein VI (GPVI) is mandatory for the initiation of integrin-mediated adhesion (8), but this concept was challenged by further mouse studies (9). Moreover, in vitro studies suggest that ...

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Section: Discussionmentioning

confidence: 81%

Section: Resultsmentioning

confidence: 95%

mentioning

confidence: 99%

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Integrin Activation State Determines Selectivity for Novel Recognition Sites in Fibrillar Collagens

Siljander¹,

Hamaia²,

Peachey³

et al. 2004

Journal of Biological Chemistry

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164

188

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“…Right: image at bottom middle magnified ϫ20 where ␣2␤1-integrin is localized to apical surface of cholangiocyte. addition, integrins are transmembrane heterodimers that activate intracellular signaling pathways (11,19). The role of the ␣ 2 ␤ 1 -integrin in cholangiocyte susceptibility to RRV infection may extend beyond simple cell-surface attachment.…”

Section: Discussionmentioning

confidence: 99%

Cholangiocyte expression of α₂β₁-integrin confers susceptibility to rotavirus-induced experimental biliary atresia

Jafri¹,

Donnelly²,

Allen³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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lation of BALB/c mice with rhesus rotavirus (RRV) in the newborn period results in biliary epithelial cell (cholangiocyte) infection and the murine model of biliary atresia. Rotavirus infection of a cell requires attachment, which is governed in part by cell-surface expression of integrins such as ␣2␤1. We hypothesized that cholangiocytes were susceptible to RRV infection because they express ␣2␤1. RRV attachment and replication was measured in cell lines derived from cholangiocytes and hepatocytes. Flow cytometry was performed on these cell lines to determine whether ␣2␤1 was present. Cholangiocytes were blocked with natural ligands, a monoclonal antibody, or small interfering RNA against the ␣2-subunit and were infected with RRV. The extrahepatic biliary tract of newborn mice was screened for the expression of the ␣2␤1-integrin. Newborn mice were pretreated with a monoclonal antibody against the ␣2-subunit and were inoculated with RRV. RRV attached and replicated significantly better in cholangiocytes than in hepatocytes. Cholangiocytes, but not hepatocytes, expressed ␣2␤1 in vitro and in vivo. Blocking assays led to a significant reduction in attachment and yield of virus in RRV-infected cholangiocytes. Pretreatment of newborn pups with an anti-␣2 monoclonal antibody reduced the ability of RRV to cause biliary atresia in mice. Cell-surface expression of the ␣2␤1-integrin plays a role in the mechanism that confers cholangiocyte susceptibility to RRV infection. rhesus rotavirus; bile ducts; cholangiopathy BILIARY ATRESIA (BA) is a unique disease of infancy in which affected children develop fibroinflammatory obliteration of the biliary tract. It is the most common indication for pediatric liver transplantation (24). Because pathogenic viruses have been found in the livers of children afflicted with biliary atresia (10,12,18,26,29), a proposed etiology for biliary atresia is perinatal infection by a virus triggering inflammatory destruction of the biliary epithelium (3,23,32). A murine model of biliary atresia (30) supports a viral pathogenesis where newborn mice infected with rhesus rotavirus (RRV) develop inflammation within the portal tract (31) and extrahepatic bile duct obstruction (9, 27).Recently, it has been shown that in the murine model of biliary atresia, RRV targeted the biliary epithelial cell (cholangiocyte) for infection (1, 31). To determine the basis for cholangiocyte susceptibility to RRV, an in vitro model of RRV infection of the two dominant cell types found within the liver (cholangiocytes and hepatocytes) was established. Consistent with the in vivo findings, RRV was better able to replicate in cholangiocytes than hepatocytes. Because the ability of rotavirus to infect cells appears to be regulated by cell-surface expression of the integrins ␣ 2 ␤ 1 , ␣ 4 ␤ 1 , ␣ v ␤ 3 , and ␣ x ␤ 2 , which serve as viral receptors (8,13,14,16,21), the cholangiocyte was surveyed for integrin expression and found to uniquely express the ␣ 2 ␤ 1 -integrin when compared with hepatocytes. Based on this informat...

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“…Early studies identified a high-affinity site within collagen type I for the I-domain of integrin ␣ 2 ␤ 1 (GFOGER, where O is hydroxyproline) (12) and a low-affinity site in collagen type III for GPVI composed of repeating GPO triplets (13). More recently, systematic analyses of human type III collagen have identified sequences that bind specific receptors.…”

Section: Use Of Collagen Peptides To Identify Receptor-binding Sitesmentioning

confidence: 99%

Structural Insights into the Interactions between Platelet Receptors and Fibrillar Collagen

Herr

Farndale

2009

Journal of Biological Chemistry

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108

100

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Collagen peptides have been used to identify binding sites for several important collagen receptors, including integrin ␣ 2 ␤ 1 , glycoprotein VI, and von Willebrand factor. In parallel, the structures of these collagen receptors have been reported, and their interactions with collagen peptides have been studied. Recently, the three-dimensional structure of the intact type I collagen fiber from rat tail tendon has been resolved by fiber diffraction. It is now possible to map the binding sites of platelet collagen receptors onto the intact collagen fiber in three dimensions. This minireview will discuss these recent findings and their implications for platelet activation by collagen. Structural Architecture of Fibrillar CollagensCollagen is the most abundant protein in the human body, where it is a vital component of the extracellular matrix and connective tissue, including blood vessels. There are 29 collagen types, of which seven (types I-III, V, XI, XXIV, and XXVII) are fibrillar, able to assemble as stable triple helices, which then form a complex higher order three-dimensional fibrous superstructure. At the simplest level, the collagen polypeptide sequence is composed of GxxЈ triplets containing glycine followed by variable residues that often include proline at position x and hydroxyproline at position xЈ. The three polypeptide chains that assemble to form a tropocollagen triple helix can be identical gene products, as for collagen III (three ␣1 chains), or may differ, as for collagen I (two ␣1 chains and one ␣2 chain). The tropocollagen triple helices assemble to form a supermolecular fiber. Studies over the past 3 decades (1-7) have established that the basic repeating unit within the collagen fiber contains five tropocollagens packed side-by-side in a pseudohexagonal arrangement, with a gap along the fiber axis between the end of one triple helix and the start of the next. This regularly repeated gap region gives rise to the characteristic banding pattern of the intact collagen fiber, with a spacing D of 67 nm between successive bands corresponding to the offset between adjacent tropocollagen molecules, the classical "quarter-stagger." The densely packed (pseudohexagonal) regions extend over nearly half (0.46D) of a single D period, whereas the gap regions occupy the remaining length of the D period (0.54D). Each collagen molecule can be divided into five D periods (Fig. 1A). Collagen fibers have a circular cross-section, suggested by fiber diffraction data to be composed of concentric layers of fibrils with a thickness of ϳ40 Å (8).In 2006, Orgel et al. (9) published the three-dimensional structure obtained using fiber diffraction of an intact collagen type I fiber from rat tail tendon. This structure revealed the complicated interdigitated arrangement of the triple helices within the collagen fiber. Each unit cell (corresponding to one D period in the mature collagen fiber) measured 678 Å long, 27 Å wide, and 40 Å deep and contained segments of five tropocollagen triple helices. As expected, a cross-s...

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Collagen-platelet interactions: recognition and signalling

Cited by 43 publications

References 48 publications

Integrin Activation State Determines Selectivity for Novel Recognition Sites in Fibrillar Collagens

Integrin Activation State Determines Selectivity for Novel Recognition Sites in Fibrillar Collagens

Cholangiocyte expression of α₂β₁-integrin confers susceptibility to rotavirus-induced experimental biliary atresia

Structural Insights into the Interactions between Platelet Receptors and Fibrillar Collagen

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Collagen-platelet interactions: recognition and signalling

Cited by 43 publications

References 48 publications

Integrin Activation State Determines Selectivity for Novel Recognition Sites in Fibrillar Collagens

Integrin Activation State Determines Selectivity for Novel Recognition Sites in Fibrillar Collagens

Cholangiocyte expression of α2β1-integrin confers susceptibility to rotavirus-induced experimental biliary atresia

Structural Insights into the Interactions between Platelet Receptors and Fibrillar Collagen

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Cholangiocyte expression of α₂β₁-integrin confers susceptibility to rotavirus-induced experimental biliary atresia