Microfibrils at Basement Membrane Zones Interact with Perlecan via Fibrillin-1

Tiedemann, Kerstin; Sasaki, Takako; Gustafsson, Erika; Göhring, Walter; Bätge, Boris; Notbohm, Holger; Timpl, Rupert; Wedel, Thilo; Schlötzer‐Schrehardt, Ursula; Reinhardt, Dieter P.

doi:10.1074/jbc.m409882200

Cited by 98 publications

(95 citation statements)

References 79 publications

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“…The perlecan core protein has been shown to associate with a range of basement membrane macromolecules including collagens (IV and XIII), laminin-1, nidogens 1 and 2, ␤1-integrin, ␣-dystroglycan, as well as fibulin-2, fibrillin-1, ECM-1, PRELP (proline-arginine-rich end leucine-rich repeat protein), fibronectin, heparin, and several growth factors (platelet-derived growth factor, FGF-2, FGF-7) and FGF-binding protein (19,(32)(33)(34)(35)(36)(37).…”

Section: Discussionmentioning

confidence: 99%

WARP Is a Novel Multimeric Component of the Chondrocyte Pericellular Matrix That Interacts with Perlecan

Allen

Bateman

Hansen³

et al. 2006

Journal of Biological Chemistry

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WARP is a novel member of the von Willebrand factor A domain superfamily of extracellular matrix proteins that is expressed by chondrocytes. WARP is restricted to the presumptive articular cartilage zone prior to joint cavitation and to the articular cartilage and fibrocartilaginous elements in the joint, spine, and sternum during mouse embryonic development. In mature articular cartilage, WARP is highly specific for the chondrocyte pericellular microenvironment and co-localizes with perlecan, a prominent component of the chondrocyte pericellular region. WARP is present in the guanidine-soluble fraction of cartilage matrix extracts as a disulfidebonded multimer, indicating that WARP is a strongly interacting component of the cartilage matrix. To investigate how WARP is integrated with the pericellular environment, we studied WARP binding to mouse perlecan using solid phase and surface plasmon resonance analysis. WARP interacts with domain III-2 of the perlecan core protein and the heparan sulfate chains of the perlecan domain I with K D values in the low nanomolar range. We conclude that WARP forms macromolecular structures that interact with perlecan to contribute to the assembly and/or maintenance of "permanent" cartilage structures during development and in mature cartilages. The extracellular matrix (ECM)3 is a complex and dynamic threedimensional environment that plays fundamental roles in morphogenesis and development, tissue structure, repair, and metastasis (1). The tissue-specific expression of collagen types and specialized ECM components results in the formation of architecturally precise interacting networks with unique functional and biological characteristics. A diverse range of ECM components have been described including more than 20 distinct collagen subtypes and a large number of proteoglycans and noncollagenous proteins. Many of these matrix proteins are modular in structure in that they are composed of protein domains, which is important in generating the multifunctionality that is characteristic of ECM proteins (2, 3). One of these domains, found in a growing number of ECM proteins involved in supramolecular structures, is the A domain first described in von Willebrand factor (VWA domain). VWA domains are found in a diverse range of ECM proteins including collagens (types VI, VII, XII, XIV, XX, XXI, XXVII, and XXVIII), matrilins, cochlin, polydom, AMACO (VWA-like domains related to those in matrilins and collagens), and the extracellular portions of nine transmembrane ␣-integrin chains (4 -6)We recently identified a new member of the von Willebrand factor A domain superfamily, WARP (von Willebrand factor A domain-related protein), that may have evolved from a collagen-like molecule (7,8). The WARP protein comprises a single N-terminal VWA domain containing a putative metal ion-dependent adhesion site motif, two fibronectin type III repeats, and a unique C-terminal segment. Our studies demonstrated WARP expression by chondrocytes, and in transfected cells WARP is a secreted glycoprotein that ...

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Section: Discussionmentioning

confidence: 99%

WARP Is a Novel Multimeric Component of the Chondrocyte Pericellular Matrix That Interacts with Perlecan

Allen

Bateman

Hansen³

et al. 2006

Journal of Biological Chemistry

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“…Generation of rabbit polyclonal anti-fibrillin-1 antibodies against the N-terminal half (␣-rFBN1-N; synonym ␣-rF16) or against the C-terminal half (␣-rFBN1-C; synonym ␣-rF6H) of human fibrillin-1 was described in detail previously (Tiedemann et al, 2001(Tiedemann et al, , 2005. For some experiments, the ␣-rFBN1-C antiserum was further purified by standard affinity chromatography using the rFBN1-C antigen.…”

Section: Antibodiesmentioning

confidence: 99%

Fibrillin Assembly Requires Fibronectin

Sabatier

Chen²,

Fagotto‐Kaufmann³

et al. 2009

MBoC

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Fibrillins constitute the major backbone of multifunctional microfibrils in elastic and nonelastic extracellular matrices. Proper assembly mechanisms are central to the formation and function of these microfibrils, and their properties are often compromised in pathological circumstances such as in Marfan syndrome and in other fibrillinopathies. Here, we have used human dermal fibroblasts to analyze the assembly of fibrillin-1 in dependence of other matrix-forming proteins. siRNA knockdown experiments demonstrated that the assembly of fibrillin-1 is strictly dependent on the presence of extracellular fibronectin fibrils. Immunolabeling performed at the light and electron microscopic level showed colocalization of fibrillin-1 with fibronectin fibrils at the early stages of the assembly process. Protein-binding assays demonstrated interactions of fibronectin with a C-terminal region of fibrillin-1, -2, and -3 and with an N-terminal region of fibrillin-1. The C-terminal half of fibrillin-2 and -3 had propensities to multimerize, as has been previously shown for fibrillin-1. The C-terminal of all three fibrillins interacted strongly with fibronectin as multimers, but not as monomers. Mapping studies revealed that the major binding interaction between fibrillins and fibronectin involves the collagen/ gelatin-binding region between domains FNI 6 and FNI 9 . INTRODUCTIONFibrillins are extracellular matrix components with important functions in elastic and nonelastic tissues including blood vessels, bone, and the eye. Fibrillins, together with the latent transforming growth factor-␤ (TGF-␤)-binding proteins (LTBPs), constitute the fibrillin-LTBP family of proteins (Hubmacher et al., 2006). Fibrillins are ϳ350 kDa in size, are disulfide-rich and glycosylated, and have a characteristic modular structure. The three human fibrillinsfibrillin-1, -2, and -3 -are encoded by different genes and are conserved at the amino acid level both in relation to one another and among species. Fibrillins are mainly composed of tandem arrays of calcium-binding epidermal growth factor-like domains interspersed with TGF-␤-binding protein domains (TB/8-Cys) and hybrid domains Hubmacher et al., 2006). Mutations in fibrillins give rise to the so-called fibrillinopathies, which include Marfan syndrome and autosomal dominant Weill-Marchesani syndrome, both caused by mutations in fibrillin-1, and Beal's syndrome, caused by mutations in fibrillin-2 (Robinson et al., 2006).High-molecular-weight, multiprotein assemblies called microfibrils are the functional units of fibrillins, which serve as a scaffold for the biogenesis of elastic fibers, confer structural integrity to individual organ systems, regulate growth factor signaling of TGF-␤-bone morphogenic protein (BMP) superfamily members and provide limited elasticity to tissues (Kielty et al., 2002;Charbonneau et al., 2004;Ramirez and Dietz, 2007). Extracted microfibrils from cell culture or tissues display a typical bead-on-a-string ultrastructure, having a 50 -55-nm periodicity when analyzed by ele...

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“…The source of the heparin that binds fibrillin-1 remains unknown. Although fibrillin-1 binds perlecan, a basement membrane heparan sulphate proteoglycan, this is a protein-protein interaction (Tiedemann et al, 2005). It is possible that fibrillin-1 interacts with heparan sulphate proteoglycan cell surface receptors, which include syndecans (Alexopoulou et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Cell adhesion to fibrillin-1: identification of an Arg-Gly-Asp-dependent synergy region and a heparin-binding site that regulates focal adhesion formation

Bax

Mahalingam

Cain

et al. 2007

Journal of Cell Science

100

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We have defined the molecular basis of cell adhesion to fibrillin-1, the major structural component of extracellular microfibrils that are associated with elastic fibres. Using human dermal fibroblasts, and recombinant domain swap fragments containing the Arg-Gly-Asp motif, we have demonstrated a requirement for upstream domains for integrin-α5β1-mediated cell adhesion and migration. An adjacent heparin-binding site, which supports focal adhesion formation, was mapped to the fibrillin-1 TB5 motif. Site-directed mutagenesis revealed two arginine residues that are crucial for heparin binding, and confirmed their role in focal adhesion formation. These integrin and syndecan adhesion motifs juxtaposed on fibrillin-1 are evolutionarily conserved and reminiscent of similar functional elements on fibronectin, highlighting their crucial functional importance.

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Microfibrils at Basement Membrane Zones Interact with Perlecan via Fibrillin-1

Cited by 98 publications

References 79 publications

WARP Is a Novel Multimeric Component of the Chondrocyte Pericellular Matrix That Interacts with Perlecan

WARP Is a Novel Multimeric Component of the Chondrocyte Pericellular Matrix That Interacts with Perlecan

Fibrillin Assembly Requires Fibronectin

Cell adhesion to fibrillin-1: identification of an Arg-Gly-Asp-dependent synergy region and a heparin-binding site that regulates focal adhesion formation

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