Fibronectin fibrillogenesis, a cell-mediated matrix assembly process.

The extracellular matrix provides a framework for cell adhesion, supports cell movement, and serves to compartmentalize tissues into functional units. Fibronectin is a core component of many extracellular matrices where it regulates a variety of cell activities through direct interactions with cell surface integrin receptors. Fibronectin is synthesized by many adherent cells which then assemble it into a fibrillar network. The assembly process is integrin-dependent and fibronectin-integrin interactions initiate a step-wise process involving conformational activation of fibronectin outside and organization of the actin cytoskeleton inside. During assembly, fibronectin undergoes conformational changes that expose fibronectin-binding sites and promote intermolecular interactions needed for fibril formation. In this review, the main steps of fibronectin assembly are described and recent studies on fibronectin conformational changes are discussed.

[1]  F. Denhez,et al.  Syndecan-4 Modulates Focal Adhesion Kinase Phosphorylation* , 2002, The Journal of Biological Chemistry.

[2]  H. Erickson,et al.  Reversible unfolding of fibronectin type III and immunoglobulin domains provides the structural basis for stretch and elasticity of titin and fibronectin. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[3]  J. Schwarzbauer,et al.  The ins and outs of fibronectin matrix assembly , 2003, Journal of Cell Science.

[4]  Kenneth M. Yamada,et al.  Taking Cell-Matrix Adhesions to the Third Dimension , 2001, Science.

[5]  W. Carter,et al.  Identification and characterization of the T lymphocyte adhesion receptor for an alternative cell attachment domain (CS-1) in plasma fibronectin , 1989, The Journal of cell biology.

[6]  J. MacLeod,et al.  Absence of the I-10 Protein Segment Mediates Restricted Dimerization of the Cartilage-specific Fibronectin Isoform* , 2002, The Journal of Biological Chemistry.

[7]  R. Hynes,et al.  Syndecan-4 signals cooperatively with integrins in a Rho-dependent manner in the assembly of focal adhesions and actin stress fibers. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[8]  M. Yi,et al.  Antiangiogenic proteins require plasma fibronectin or vitronectin for in vivo activity , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Viola Vogel,et al.  Structural changes of fibronectin adsorbed to model surfaces probed by fluorescence resonance energy transfer. , 2004, Journal of biomedical materials research. Part A.

[10]  I. Singer The fibronexus: a transmembrane association of fibronectin-containing fibers and bundles of 5 nm microfilaments in hamster and human fibroblasts , 1979, Cell.

[11]  Kamin J. Johnson,et al.  The Compact Conformation of Fibronectin Is Determined by Intramolecular Ionic Interactions* , 1999, The Journal of Biological Chemistry.

[12]  Viola Vogel,et al.  Fibronectin extension and unfolding within cell matrix fibrils controlled by cytoskeletal tension , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[13]  J. Schwarzbauer,et al.  A novel fibronectin binding site required for fibronectin fibril growth during matrix assembly , 2001, The Journal of cell biology.

[14]  P. Janmey,et al.  Conformational states of fibronectin. Effects of pH, ionic strength, and collagen binding. , 1982, The Journal of biological chemistry.

[15]  J. Schwarzbauer,et al.  Regulatory Role for Src and Phosphatidylinositol 3-Kinase in Initiation of Fibronectin Matrix Assembly* , 2002, The Journal of Biological Chemistry.

[16]  Hector H. Huang,et al.  Mechanical unfolding intermediates observed by single-molecule force spectroscopy in a fibronectin type III module. , 2005, Journal of molecular biology.

[17]  J. Schwarzbauer,et al.  Modulation of Cell‐Extracellular Matrix Interactions a , 1998, Annals of the New York Academy of Sciences.

[18]  C. Damsky,et al.  FAK promotes organization of fibronectin matrix and fibrillar adhesions , 2004, Journal of Cell Science.

[19]  I. Campbell,et al.  Interdomain Tilt Angle Determines Integrin-dependent Function of the Ninth and Tenth FIII Domains of Human Fibronectin* , 2004, Journal of Biological Chemistry.

[20]  I. Campbell,et al.  Solution structure of a type 2 module from fibronectin: implications for the structure and function of the gelatin-binding domain. , 1997, Structure.

[21]  J. Schwarzbauer,et al.  Modulatory roles for integrin activation and the synergy site of fibronectin during matrix assembly. , 1997, Molecular biology of the cell.

[22]  R. Hynes,et al.  Defects in mesoderm, neural tube and vascular development in mouse embryos lacking fibronectin. , 1993, Development.

[23]  E Ruoslahti,et al.  New perspectives in cell adhesion: RGD and integrins. , 1987, Science.

[24]  E Ruoslahti,et al.  Crystal structure of the tenth type III cell adhesion module of human fibronectin. , 1994, Journal of molecular biology.

[25]  E. Ruoslahti,et al.  A fibronectin self-assembly site involved in fibronectin matrix assembly: reconstruction in a synthetic peptide , 1992, The Journal of cell biology.

[26]  E. Ruoslahti,et al.  Crystals of the cell-binding module of fibronectin obtained from a series of recombinant fragments differing in length. , 1994, Journal of molecular biology.

[27]  J. Schwarzbauer,et al.  Five type I modules of fibronectin form a functional unit that binds to fibroblasts and Staphylococcus aureus. , 1991, The Journal of biological chemistry.

[28]  R. Hynes,et al.  The dynamic dialogue between cells and matrices: implications of fibronectin's elasticity. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[29]  J. Schwarzbauer,et al.  Stimulatory effects of a three-dimensional microenvironment on cell-mediated fibronectin fibrillogenesis , 2005, Journal of Cell Science.

[30]  J. Schwarzbauer Identification of the fibronectin sequences required for assembly of a fibrillar matrix , 1991, The Journal of cell biology.

[31]  Klaus Schulten,et al.  Identifying unfolding intermediates of FN-III(10) by steered molecular dynamics. , 2002, Journal of molecular biology.

[32]  J. Schwarzbauer,et al.  Altered rate of fibronectin matrix assembly by deletion of the first type III repeats , 1996, The Journal of cell biology.

[33]  J. Schwarzbauer,et al.  Control of Cell Cycle Progression by Fibronectin Matrix Architecture* , 1998, The Journal of Biological Chemistry.

[34]  J. Peters,et al.  Deletion of the alternatively spliced fibronectin EIIIA domain in mice reduces atherosclerosis. , 2004, Blood.

[35]  K. Yamada,et al.  Inhibition of binding of fibronectin to matrix assembly sites by anti- integrin (alpha 5 beta 1) antibodies , 1990, The Journal of cell biology.

[36]  J. Schwarzbauer,et al.  A novel RGD-independent fibronectin assembly pathway initiated by alpha4beta1 integrin binding to the alternatively spliced V region. , 2000, Journal of cell science.

[37]  J. MacLeod,et al.  Fibronectin mRNA Splice Variant in Articular Cartilage Lacks Bases Encoding the V, III-15, and I-10 Protein Segments* , 1996, The Journal of Biological Chemistry.

[38]  M. Yi,et al.  A fibronectin fragment inhibits tumor growth, angiogenesis, and metastasis. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[39]  K. Sekiguchi,et al.  Recombinant Expression and Characterization of a Novel Fibronectin Isoform Expressed in Cartilaginous Tissues* , 2003, Journal of Biological Chemistry.

[40]  K. Constantine,et al.  Refined solution structure and ligand-binding properties of PDC-109 domain b. A collagen-binding type II domain. , 1992, Journal of molecular biology.

[41]  M Karplus,et al.  Forced unfolding of fibronectin type 3 modules: an analysis by biased molecular dynamics simulations. , 1999, Journal of molecular biology.

[42]  K. Burridge,et al.  Rho-mediated Contractility Exposes a Cryptic Site in Fibronectin and Induces Fibronectin Matrix Assembly , 1998, The Journal of cell biology.

[43]  R. Hynes,et al.  Multiple sites of alternative splicing of the rat fibronectin gene transcript. , 1987, The EMBO journal.

[44]  A. Kornblihtt,et al.  Regulation of fibronectin splicing in sinusoidal endothelial cells from normal or injured liver , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[45]  Kenneth M. Yamada,et al.  Transmembrane crosstalk between the extracellular matrix and the cytoskeleton , 2001, Nature Reviews Molecular Cell Biology.

[46]  Kenneth M. Yamada,et al.  Integrin Dynamics and Matrix Assembly: Tensin-Dependent Translocation of α5β1 Integrins Promotes Early Fibronectin Fibrillogenesis , 2000 .

[47]  Benjamin Geiger,et al.  Dynamics and segregation of cell–matrix adhesions in cultured fibroblasts , 2000, Nature Cell Biology.

[48]  H. Erickson,et al.  Fibronectin in extended and compact conformations. Electron microscopy and sedimentation analysis. , 1983, The Journal of biological chemistry.

[49]  J. Erickson,et al.  Model of fibronectin tertiary structure based on studies of interactions between fragments. , 1986, Biochemistry.

[50]  S. Aota,et al.  Formation of amyloid-like fibrils by self-association of a partially unfolded fibronectin type III module. , 1998, Journal of molecular biology.

[51]  S. Tumova,et al.  Heparan Sulfate Chains from Glypican and Syndecans Bind the Hep II Domain of Fibronectin Similarly Despite Minor Structural Differences* , 2000, The Journal of Biological Chemistry.

[52]  K. O. Mercurius,et al.  Cell adhesion and signaling on the fibronectin 1st type III repeat; requisite roles for cell surface proteoglycans and integrins , 2001, BMC Cell Biology.

[53]  J. Schwarzbauer,et al.  Coordinated regulation of fibronectin fibril assembly and actin stress fiber formation. , 1997, Cell adhesion and communication.

[54]  D. Hocking,et al.  Fibronectin polymerization regulates the composition and stability of extracellular matrix fibrils and cell-matrix adhesions. , 2002, Molecular biology of the cell.

[55]  V. Koteliansky,et al.  Monoclonal antibody to fibronectin which inhibits extracellular matrix assembly , 1987, FEBS letters.

[56]  J. Brugge,et al.  Sensing the environment: a historical perspective on integrin signal transduction , 2002, Nature Cell Biology.

[57]  E. Ruoslahti,et al.  Superfibronectin is a functionally distinct form of fibronectin , 1994, Nature.

[58]  M. Rief,et al.  The mechanical stability of immunoglobulin and fibronectin III domains in the muscle protein titin measured by atomic force microscopy. , 1998, Biophysical journal.

[59]  V. Vogel,et al.  Coexisting conformations of fibronectin in cell culture imaged using fluorescence resonance energy transfer , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[60]  J. Schwarzbauer,et al.  Tenascin-C Suppresses Rho Activation , 2000, The Journal of cell biology.

[61]  P. McKeown-Longo,et al.  Fibronectin's III-1 module contains a conformation-dependent binding site for the amino-terminal region of fibronectin. , 1994, The Journal of biological chemistry.

[62]  Richard O. Hynes,et al.  Lymphoid cells recognize an alternatively spliced segment of fibronectin via the integrin receptor α 4 β 1 , 1990, Cell.

[63]  M. Carson,et al.  Dependence of the shape of the plasma fibronectin molecule on solvent composition. Ionic strength and glycerol content. , 1983, The Journal of biological chemistry.

[64]  S. Aota,et al.  Monoclonal antibody characterization of two distant sites required for function of the central cell-binding domain of fibronectin in cell adhesion, cell migration, and matrix assembly , 1991, The Journal of cell biology.

[65]  I D Campbell,et al.  Solution structure of the N-terminal F1 module pair from human fibronectin. , 1999, Biochemistry.

[66]  D. Sheppard,et al.  The EIIIA Segment of Fibronectin Is a Ligand for Integrins α9β1 and α4β1Providing a Novel Mechanism for Regulating Cell Adhesion by Alternative Splicing* , 2002, The Journal of Biological Chemistry.

[67]  M. Ginsberg,et al.  Identification of a New Biological Function for the Integrin αvβ3: Initiation of Fibronectin Matrix Assembly , 1996 .

[68]  Jonathan Boyd,et al.  The three-dimensional structure of the tenth type III module of fibronectin: An insight into RGD-mediated interactions , 1992, Cell.

[69]  R. Albrecht,et al.  Modulation of cell surface fibronectin assembly sites by lysophosphatidic acid , 1994, The Journal of cell biology.

[70]  D. Mosher,et al.  Assembly of fibronectin into extracellular matrix. , 1993, Annals of the New York Academy of Sciences.

[71]  K. Sekiguchi,et al.  Mice lacking the EDB segment of fibronectin develop normally but exhibit reduced cell growth and fibronectin matrix assembly in vitro. , 2002, Cancer research.

[72]  P. McKeown-Longo,et al.  The Receptor for Urokinase-type Plasminogen Activator Regulates Fibronectin Matrix Assembly in Human Skin Fibroblasts* , 2004, Journal of Biological Chemistry.

[73]  M. Ginsberg,et al.  Integrin activation and cytoskeletal interaction are essential for the assembly of a fibronectin matrix , 1995, Cell.

[74]  J. Sottile,et al.  Identification of Protein-disulfide Isomerase Activity in Fibronectin* , 1999, The Journal of Biological Chemistry.

[75]  J. Sottile,et al.  Fibronectin matrix turnover occurs through a caveolin-1-dependent process. , 2004, Molecular biology of the cell.

[76]  J. Schwarzbauer Alternative splicing of fibronectin: Three variants, three functions , 1991, BioEssays : news and reviews in molecular, cellular and developmental biology.

[77]  P. McKeown-Longo,et al.  Interaction of the 70,000-mol-wt amino-terminal fragment of fibronectin with the matrix-assembly receptor of fibroblasts , 1985, The Journal of cell biology.

[78]  M. K. Magnússon,et al.  Lysophosphatidic acid and microtubule-destabilizing agents stimulate fibronectin matrix assembly through Rho-dependent actin stress fiber formation and cell contraction. , 1997, Molecular biology of the cell.

[79]  Kamin J. Johnson,et al.  Plasma fibronectin supports neuronal survival and reduces brain injury following transient focal cerebral ischemia but is not essential for skin-wound healing and hemostasis. , 2001, Nature Medicine.

[80]  K. Wennerberg,et al.  Beta 1 integrin-dependent and -independent polymerization of fibronectin , 1996, The Journal of cell biology.

[81]  D. Hoyt,et al.  Anastellin, an FN3 fragment with fibronectin polymerization activity, resembles amyloid fibril precursors. , 2003, Journal of molecular biology.

[82]  N. Boudreau,et al.  Extracellular matrix and integrin signalling: the shape of things to come. , 1999, The Biochemical journal.

[83]  I. Campbell,et al.  Structure of the fibronectin type 1 module , 1990, Nature.

[84]  J. Schwarzbauer,et al.  Fibronectin self-association is mediated by complementary sites within the amino-terminal one-third of the molecule. , 1994, The Journal of biological chemistry.

[85]  Mariano Carrion-Vazquez,et al.  The mechanical hierarchies of fibronectin observed with single-molecule AFM. , 2002, Journal of molecular biology.

[86]  E. Raines,et al.  The extracellular matrix can regulate vascular cell migration, proliferation, and survival: relationships to vascular disease , 2000, International journal of experimental pathology.

[87]  Harold P. Erickson,et al.  2.0 Å Crystal Structure of a Four-Domain Segment of Human Fibronectin Encompassing the RGD Loop and Synergy Region , 1996, Cell.

[88]  D. Mosher,et al.  Assembly of Exogenous Fibronectin by Fibronectin-null Cells Is Dependent on the Adhesive Substrate* , 2004, Journal of Biological Chemistry.

[89]  R. Segal,et al.  Studies on intercellular LETS glycoprotein matrices , 1978, Cell.

[90]  Virgil L. Woods,et al.  A polymeric form of fibronectin has antimetastatic effects against multiple tumor types , 1996, Nature Medicine.

[91]  Jeffrey W. Smith,et al.  Identification of a novel integrin binding site in fibronectin. Differential utilization by beta 3 integrins. , 1994, The Journal of biological chemistry.

[92]  J. Xiong,et al.  Regulation of α5β1 integrin conformation and function by urokinase receptor binding , 2005, The Journal of cell biology.

[93]  Klaus Schulten,et al.  Structure and functional significance of mechanically unfolded fibronectin type III1 intermediates , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[94]  S. Brew,et al.  Cryptic Self-association Sites in Type III Modules of Fibronectin* , 1997, The Journal of Biological Chemistry.

[95]  P. Bjorkman,et al.  Crystal structure of tandem type III fiibronectin domains from drosophila neuroglian at 2.0 å , 1994, Neuron.

[96]  J. Clarke,et al.  Folding and stability of a fibronectin type III domain of human tenascin. , 1997, Journal of molecular biology.

[97]  D. Mosher,et al.  Formation of Sodium Dodecyl Sulfate-stable Fibronectin Multimers , 1996, The Journal of Biological Chemistry.

[98]  D. M. Peters,et al.  Fibronectin Fibrillogenesis Involves the Heparin II Binding Domain of Fibronectin* , 1998, The Journal of Biological Chemistry.

[99]  H. Erickson,et al.  Dynamics and elasticity of the fibronectin matrix in living cell culture visualized by fibronectin-green fluorescent protein. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[100]  A. Chauhan,et al.  Regulated splicing of the fibronectin EDA exon is essential for proper skin wound healing and normal lifespan , 2003, The Journal of cell biology.

[101]  B. Quade,et al.  Fibronectin's cell-adhesive domain and an amino-terminal matrix assembly domain participate in its assembly into fibroblast pericellular matrix. , 1987, The Journal of biological chemistry.

[102]  R. Hynes,et al.  Role of disulfide bonds in the attachment and function of large, external, transformation-sensitive glycoprotein at the cell surface. , 1978, Biochimica et biophysica acta.

[103]  H. Erickson,et al.  Dual labeling of the fibronectin matrix and actin cytoskeleton with green fluorescent protein variants. , 2002, Journal of cell science.

[104]  V. Koteliansky,et al.  Role of the I-9 and III-1 modules of fibronectin in formation of an extracellular fibronectin matrix. , 1991, The Journal of biological chemistry.

[105]  Urea-induced sequential unfolding of fibronectin: a fluorescence spectroscopy and circular dichroism study. , 2004, Biochemistry.