DOI: 10.1073/pnas.96.6.2805. Syndecan-4 signals cooperatively with integrins in a Rhodependent manner in the assembly of focal adhesions and actin stress fibers

Syndecan-4 signals cooperatively with integrins in a Rhodependent manner in the assembly of focal adhesions and actin stress fibers

10.1073/pnas.96.6.2805

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The assembly of focal adhesions and actin stress fibers by cells plated on fibronectin depends on adhesion-mediated signals involving both integrins and cell-surface heparan sulfate proteoglycans. These two cell-surface receptors interact with different domains of fibronectin. To attempt to identify the heparan sulfate proteoglycans involved, we used fibronectin-null (FN−/−) mouse fibroblasts to eliminate the contribution of endogenous fibronectin during the analysis. FN−/− fibroblasts plated on the cell-binding domain of fibronectin or on antibodies directed against mouse β1 integrin chains attach but fail to spread and do not form focal adhesions or actin stress fibers. When such cells are treated with antibodies directed against the ectodomain of mouse syndecan-4, they spread fully and assemble focal adhesions and actin stress fibers indistinguishable from those seen in cells plated on intact fibronectin. These results identify syndecan-4 as a heparan sulfate proteoglycan involved in the assembly process. The antibody-stimulated assembly of focal adhesions and actin stress fibers in cells plated on the cell-binding domain of fibronectin can be blocked with C3 exotransferase, an inhibitor of the small GTP-binding protein Rho. Treatment of cells with lysophosphatidic acid, which activates Rho, results in full spreading and assembly of focal adhesions and actin stress fibers in fibroblasts plated on the cell-binding domain of fibronectin. We conclude that syndecan-4 and integrins can act cooperatively in generating signals for cell spreading and for the assembly of focal adhesions and actin stress fibers. We conclude further that these joint signals are regulated in a Rho-dependent manner.

Bibliography

Saoncella, S., Echtermeyer, F., Denhez, F., Nowlen, J. K., Mosher, D. F., Robinson, S. D., Hynes, R. O., & Goetinck, P. F. (1999). Syndecan-4 signals cooperatively with integrins in a Rhodependent manner in the assembly of focal adhesions and actin stress fibers. Proceedings of the National Academy of Sciences, 96(6), 2805â2810.

Authors 8

Stefania Saoncella (first)
Frank Echtermeyer (additional)
Fabienne Denhez (additional)
Julie K. Nowlen (additional)
Deane F. Mosher (additional)
Stephen D. Robinson (additional)
Richard O. Hynes (additional)
Paul F. Goetinck (additional)

References 33 Referenced 308

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:35 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 5:50 p.m.)
Indexed	2 days, 20 hours ago (Sept. 3, 2025, 6:55 a.m.)
Issued	26 years, 5 months ago (March 16, 1999)
Published	26 years, 5 months ago (March 16, 1999)
Published Online	26 years, 5 months ago (March 16, 1999)
Published Print	26 years, 5 months ago (March 16, 1999)

Funders 0

None

BibTeX

@article{Saoncella_1999, title={Syndecan-4 signals cooperatively with integrins in a Rhodependent manner in the assembly of focal adhesions and actin stress fibers}, volume={96}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.96.6.2805}, DOI={10.1073/pnas.96.6.2805}, number={6}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Saoncella, Stefania and Echtermeyer, Frank and Denhez, Fabienne and Nowlen, Julie K. and Mosher, Deane F. and Robinson, Stephen D. and Hynes, Richard O. and Goetinck, Paul F.}, year={1999}, month=mar, pages={2805–2810} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        9,
        3
      ]
    ],
    "date-time": "2025-09-03T10:55:03Z",
    "timestamp": 1756896903361
  },
  "reference-count": 33,
  "publisher": "Proceedings of the National Academy of Sciences",
  "issue": "6",
  "content-domain": {
    "domain": [
      "www.pnas.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        1999,
        3,
        16
      ]
    ]
  },
  "abstract": "<jats:p>The assembly of focal adhesions and actin stress fibers by cells plated on fibronectin depends on adhesion-mediated signals involving both integrins and cell-surface heparan sulfate proteoglycans. These two cell-surface receptors interact with different domains of fibronectin. To attempt to identify the heparan sulfate proteoglycans involved, we used fibronectin-null (FN\u2212/\u2212) mouse fibroblasts to eliminate the contribution of endogenous fibronectin during the analysis. FN\u2212/\u2212 fibroblasts plated on the cell-binding domain of fibronectin or on antibodies directed against mouse \u03b21 integrin chains attach but fail to spread and do not form focal adhesions or actin stress fibers. When such cells are treated with antibodies directed against the ectodomain of mouse syndecan-4, they spread fully and assemble focal adhesions and actin stress fibers indistinguishable from those seen in cells plated on intact fibronectin. These results identify syndecan-4 as a heparan sulfate proteoglycan involved in the assembly process. The antibody-stimulated assembly of focal adhesions and actin stress fibers in cells plated on the cell-binding domain of fibronectin can be blocked with C3 exotransferase, an inhibitor of the small GTP-binding protein Rho. Treatment of cells with lysophosphatidic acid, which activates Rho, results in full spreading and assembly of focal adhesions and actin stress fibers in fibroblasts plated on the cell-binding domain of fibronectin. We conclude that syndecan-4 and integrins can act cooperatively in generating signals for cell spreading and for the assembly of focal adhesions and actin stress fibers. We conclude further that these joint signals are regulated in a Rho-dependent manner.</jats:p>",
  "DOI": "10.1073/pnas.96.6.2805",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2002,
        7,
        26
      ]
    ],
    "date-time": "2002-07-26T14:35:07Z",
    "timestamp": 1027694107000
  },
  "page": "2805-2810",
  "update-policy": "http://dx.doi.org/10.1073/pnas.cm10313",
  "source": "Crossref",
  "is-referenced-by-count": 308,
  "title": "Syndecan-4 signals cooperatively with integrins in a Rhodependent manner in the assembly of focal adhesions and actin stress fibers",
  "prefix": "10.1073",
  "volume": "96",
  "author": [
    {
      "given": "Stefania",
      "family": "Saoncella",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129; Department of Medicine, University of Wisconsin, Madison, WI 53706; Howard Hughes Medical Institute and Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139"
        }
      ]
    },
    {
      "given": "Frank",
      "family": "Echtermeyer",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129; Department of Medicine, University of Wisconsin, Madison, WI 53706; Howard Hughes Medical Institute and Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139"
        }
      ]
    },
    {
      "given": "Fabienne",
      "family": "Denhez",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129; Department of Medicine, University of Wisconsin, Madison, WI 53706; Howard Hughes Medical Institute and Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139"
        }
      ]
    },
    {
      "given": "Julie K.",
      "family": "Nowlen",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129; Department of Medicine, University of Wisconsin, Madison, WI 53706; Howard Hughes Medical Institute and Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139"
        }
      ]
    },
    {
      "given": "Deane F.",
      "family": "Mosher",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129; Department of Medicine, University of Wisconsin, Madison, WI 53706; Howard Hughes Medical Institute and Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139"
        }
      ]
    },
    {
      "given": "Stephen D.",
      "family": "Robinson",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129; Department of Medicine, University of Wisconsin, Madison, WI 53706; Howard Hughes Medical Institute and Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139"
        }
      ]
    },
    {
      "given": "Richard O.",
      "family": "Hynes",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129; Department of Medicine, University of Wisconsin, Madison, WI 53706; Howard Hughes Medical Institute and Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139"
        }
      ]
    },
    {
      "given": "Paul F.",
      "family": "Goetinck",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129; Department of Medicine, University of Wisconsin, Madison, WI 53706; Howard Hughes Medical Institute and Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139"
        }
      ]
    }
  ],
  "member": "341",
  "published-online": {
    "date-parts": [
      [
        1999,
        3,
        16
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_3_3_1_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1242/dev.117.4.1183"
    },
    {
      "key": "e_1_3_3_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/dbio.1996.0317"
    },
    {
      "key": "e_1_3_3_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(00)81279-9"
    },
    {
      "key": "e_1_3_3_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0955-0674(97)80123-8"
    },
    {
      "key": "e_1_3_3_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0955-0674(98)80144-0"
    },
    {
      "key": "e_1_3_3_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.cellbio.12.1.463"
    },
    {
      "key": "e_1_3_3_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.7716514"
    },
    {
      "key": "e_1_3_3_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(92)90115-S"
    },
    {
      "key": "e_1_3_3_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.cb.11.110195.003001"
    },
    {
      "key": "e_1_3_3_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1986.tb04265.x"
    },
    {
      "key": "e_1_3_3_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.7846531"
    },
    {
      "key": "e_1_3_3_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.131.3.791"
    },
    {
      "key": "e_1_3_3_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0955-0674(96)80059-7"
    },
    {
      "key": "e_1_3_3_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0955-0674(97)80156-1"
    },
    {
      "key": "e_1_3_3_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.142.2.573"
    },
    {
      "key": "e_1_3_3_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1091/mbc.5.2.183"
    },
    {
      "key": "e_1_3_3_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1091/mbc.6.11.1503"
    },
    {
      "key": "e_1_3_3_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1242/dev.119.4.1079"
    },
    {
      "key": "e_1_3_3_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.128.5.979"
    },
    {
      "key": "e_1_3_3_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.141.2.527"
    },
    {
      "key": "e_1_3_3_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/oxfordjournals.jbchem.a021724"
    },
    {
      "key": "e_1_3_3_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.79.3.917"
    },
    {
      "key": "e_1_3_3_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0021-9258(17)42405-7"
    },
    {
      "key": "e_1_3_3_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.271.4.2071"
    },
    {
      "key": "e_1_3_3_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/mcb.12.5.2391-2395.1992"
    },
    {
      "key": "e_1_3_3_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(92)90611-F"
    },
    {
      "key": "e_1_3_3_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.272.18.11805"
    },
    {
      "key": "e_1_3_3_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.272.13.8133"
    },
    {
      "key": "e_1_3_3_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.273.17.10624"
    },
    {
      "key": "e_1_3_3_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1242/jcs.101.2.277"
    },
    {
      "key": "e_1_3_3_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.94.25.13683"
    },
    {
      "key": "e_1_3_3_32_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.142.1.129"
    },
    {
      "key": "e_1_3_3_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.142.1.139"
    }
  ],
  "container-title": "Proceedings of the National Academy of Sciences",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://pnas.org/doi/pdf/10.1073/pnas.96.6.2805",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2022,
        4,
        13
      ]
    ],
    "date-time": "2022-04-13T21:50:31Z",
    "timestamp": 1649886631000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://pnas.org/doi/full/10.1073/pnas.96.6.2805"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1999,
        3,
        16
      ]
    ]
  },
  "references-count": 33,
  "journal-issue": {
    "issue": "6",
    "published-print": {
      "date-parts": [
        [
          1999,
          3,
          16
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1073/pnas.96.6.2805"
  ],
  "URL": "http://dx.doi.org/10.1073/pnas.96.6.2805",
  "relation": {},
  "ISSN": [
    "0027-8424",
    "1091-6490"
  ],
  "subject": [],
  "container-title-short": "Proc. Natl. Acad. Sci. U.S.A.",
  "published": {
    "date-parts": [
      [
        1999,
        3,
        16
      ]
    ]
  },
  "assertion": [
    {
      "value": "1998-12-31",
      "order": 1,
      "name": "accepted",
      "label": "Accepted",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "1999-03-16",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}