DOI: 10.1073/pnas.96.17.9648. Wiskott-Aldrich syndrome protein regulates podosomes in primary human macrophages

Wiskott-Aldrich syndrome protein regulates podosomes in primary human macrophages

10.1073/pnas.96.17.9648

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Wiskott-Aldrich syndrome protein (WASp) is a hematopoietic-specific, multidomain protein whose mutation is responsible for the immunodeficiency disorder Wiskott-Aldrich syndrome. WASp contains a binding motif for the Rho GTPase CDC42Hs as well as verprolin/cofilin-like actin-regulatory domains, but no specific actin structure regulated by CDC42Hs-WASp has been identified. We found that WASp colocalizes with CDC42Hs and actin in the core of podosomes, a highly dynamic adhesion structure of human blood-derived macrophages. Microinjection of constitutively active V12CDC42Hs or a constitutively active WASp fragment consisting of the verprolin/cofilin-like domains led to the disassemly of podosomes. Conversely, macrophages from patients expressing truncated forms of WASp completely lacked podosomes. These findings indicate that WASp controls podosome assembly and, in cooperation with CDC42Hs, podosome disassembly in primary human macrophages.

Bibliography

Linder, S., Nelson, D., Weiss, M., & Aepfelbacher, M. (1999). Wiskott-Aldrich syndrome protein regulates podosomes in primary human macrophages. Proceedings of the National Academy of Sciences, 96(17), 9648â9653.

Authors 4

Stefan Linder (first)
David Nelson (additional)
Michael Weiss (additional)
Martin Aepfelbacher (additional)

References 38 Referenced 356

10.1016/S1357-4310(98)01268-4
10.1182/blood.V68.6.1329.1329
10.1182/blood.V87.7.2621.bloodjournal8772621
10.1007/BF00792601
10.1002/(SICI)1521-4141(199810)28:10<3259::AID-IMMU3259>3.0.CO;2-B
R Badolato, S Sozzani, F Malacarne, S Bresciani, M Fiorini, A Borsatti, A Albertini, A Mantovani, A Ugazio, L D Notarangelo J Immunol 161, 1026–1033 (1998). (10.4049/jimmunol.161.2.1026) / J Immunol by Badolato R (1998)
10.1046/j.1365-2141.1998.00767.x
10.1016/0092-8674(94)90528-2
10.1007/s004390050162
10.1016/S0960-9822(02)00423-2
10.1073/pnas.93.11.5615
10.1016/S0092-8674(00)81050-8
10.1002/j.1460-2075.1996.tb00917.x
10.1093/emboj/17.23.6932
10.1126/science.279.5350.509
10.1073/pnas.94.26.14671
10.1016/S0960-9822(98)00015-3
10.1074/jbc.273.10.5765
10.1006/bbrc.1997.8064
10.1038/34208
10.1182/blood.V90.8.3089
10.1073/pnas.91.10.4263
10.1016/0092-8674(92)90163-7
M Aepfelbacher, M Essler, E Huber, A Czech, P C Weber J Immunol 157, 5070–5075 (1996). (10.4049/jimmunol.157.11.5070) / J Immunol by Aepfelbacher M (1996)
10.1172/JCI118712
10.1016/S0014-4827(85)80044-6
10.1128/MCB.15.10.5725
10.1016/S0021-9258(18)54786-4
10.1242/jcs.109.2.367
10.1083/jcb.104.6.1521
10.1016/8756-3282(90)90082-A
10.1016/0014-4827(87)90238-2
10.1002/cm.970300405
10.1242/jcs.104.2.595
10.1083/jcb.98.4.1546
10.1093/emboj/18.3.501
10.1016/S0167-5699(98)01350-4
E Schuuring, E Verhoeven, S Litvinov, R J Michalides Mol Cell Biol 13, 2981–2898 (1993). / Mol Cell Biol by Schuuring E (1993)

Dates

Type	When
Created	23 years ago (July 26, 2002, 10:32 a.m.)
Deposited	2 years, 4 months ago (April 22, 2023, 8:09 a.m.)
Indexed	1 month, 1 week ago (July 16, 2025, 8:16 a.m.)
Issued	26 years ago (Aug. 17, 1999)
Published	26 years ago (Aug. 17, 1999)
Published Online	26 years ago (Aug. 17, 1999)
Published Print	26 years ago (Aug. 17, 1999)

Funders 0

None

BibTeX

@article{Linder_1999, title={Wiskott-Aldrich syndrome protein regulates podosomes in primary human macrophages}, volume={96}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.96.17.9648}, DOI={10.1073/pnas.96.17.9648}, number={17}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Linder, Stefan and Nelson, David and Weiss, Michael and Aepfelbacher, Martin}, year={1999}, month=aug, pages={9648–9653} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        7,
        16
      ]
    ],
    "date-time": "2025-07-16T12:16:54Z",
    "timestamp": 1752668214206
  },
  "reference-count": 38,
  "publisher": "Proceedings of the National Academy of Sciences",
  "issue": "17",
  "content-domain": {
    "domain": [
      "www.pnas.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        1999,
        8,
        17
      ]
    ]
  },
  "abstract": "<jats:p>Wiskott-Aldrich syndrome protein (WASp) is a hematopoietic-specific, multidomain protein whose mutation is responsible for the immunodeficiency disorder Wiskott-Aldrich syndrome. WASp contains a binding motif for the Rho GTPase CDC42Hs as well as verprolin/cofilin-like actin-regulatory domains, but no specific actin structure regulated by CDC42Hs-WASp has been identified. We found that WASp colocalizes with CDC42Hs and actin in the core of podosomes, a highly dynamic adhesion structure of human blood-derived macrophages. Microinjection of constitutively active V12CDC42Hs or a constitutively active WASp fragment consisting of the verprolin/cofilin-like domains led to the disassemly of podosomes. Conversely, macrophages from patients expressing truncated forms of WASp completely lacked podosomes. These findings indicate that WASp controls podosome assembly and, in cooperation with CDC42Hs, podosome disassembly in primary human macrophages.</jats:p>",
  "DOI": "10.1073/pnas.96.17.9648",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2002,
        7,
        26
      ]
    ],
    "date-time": "2002-07-26T14:32:33Z",
    "timestamp": 1027693953000
  },
  "page": "9648-9653",
  "update-policy": "http://dx.doi.org/10.1073/pnas.cm10313",
  "source": "Crossref",
  "is-referenced-by-count": 356,
  "title": "Wiskott-Aldrich syndrome protein regulates podosomes in primary human macrophages",
  "prefix": "10.1073",
  "volume": "96",
  "author": [
    {
      "given": "Stefan",
      "family": "Linder",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Max von Pettenkofer-Institut f\u00fcr Medizinische Mikrobiologie and Institut f\u00fcr Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Pettenkoferstrasse 9a, Ludwig-Maximilians-Universit\u00e4t, 80336 Munich, Germany; National Cancer Institute, Metabolism Branch, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892; and Dr. von Haunersches Kinderspital, Klinikum Innenstadt, Lindwurmstrasse 4, 80337 Munich, Germany"
        }
      ]
    },
    {
      "given": "David",
      "family": "Nelson",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Max von Pettenkofer-Institut f\u00fcr Medizinische Mikrobiologie and Institut f\u00fcr Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Pettenkoferstrasse 9a, Ludwig-Maximilians-Universit\u00e4t, 80336 Munich, Germany; National Cancer Institute, Metabolism Branch, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892; and Dr. von Haunersches Kinderspital, Klinikum Innenstadt, Lindwurmstrasse 4, 80337 Munich, Germany"
        }
      ]
    },
    {
      "given": "Michael",
      "family": "Weiss",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Max von Pettenkofer-Institut f\u00fcr Medizinische Mikrobiologie and Institut f\u00fcr Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Pettenkoferstrasse 9a, Ludwig-Maximilians-Universit\u00e4t, 80336 Munich, Germany; National Cancer Institute, Metabolism Branch, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892; and Dr. von Haunersches Kinderspital, Klinikum Innenstadt, Lindwurmstrasse 4, 80337 Munich, Germany"
        }
      ]
    },
    {
      "given": "Martin",
      "family": "Aepfelbacher",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Max von Pettenkofer-Institut f\u00fcr Medizinische Mikrobiologie and Institut f\u00fcr Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Pettenkoferstrasse 9a, Ludwig-Maximilians-Universit\u00e4t, 80336 Munich, Germany; National Cancer Institute, Metabolism Branch, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892; and Dr. von Haunersches Kinderspital, Klinikum Innenstadt, Lindwurmstrasse 4, 80337 Munich, Germany"
        }
      ]
    }
  ],
  "member": "341",
  "published-online": {
    "date-parts": [
      [
        1999,
        8,
        17
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_3_3_1_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S1357-4310(98)01268-4"
    },
    {
      "key": "e_1_3_3_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1182/blood.V68.6.1329.1329"
    },
    {
      "key": "e_1_3_3_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1182/blood.V87.7.2621.bloodjournal8772621"
    },
    {
      "key": "e_1_3_3_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/BF00792601"
    },
    {
      "key": "e_1_3_3_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/(SICI)1521-4141(199810)28:10<3259::AID-IMMU3259>3.0.CO;2-B"
    },
    {
      "key": "e_1_3_3_6_2",
      "doi-asserted-by": "crossref",
      "first-page": "1026",
      "DOI": "10.4049/jimmunol.161.2.1026",
      "volume": "161",
      "author": "Badolato R",
      "year": "1998",
      "unstructured": "R Badolato, S Sozzani, F Malacarne, S Bresciani, M Fiorini, A Borsatti, A Albertini, A Mantovani, A Ugazio, L D Notarangelo J Immunol 161, 1026\u20131033 (1998).",
      "journal-title": "J Immunol"
    },
    {
      "key": "e_1_3_3_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1046/j.1365-2141.1998.00767.x"
    },
    {
      "key": "e_1_3_3_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(94)90528-2"
    },
    {
      "key": "e_1_3_3_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/s004390050162"
    },
    {
      "key": "e_1_3_3_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0960-9822(02)00423-2"
    },
    {
      "key": "e_1_3_3_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.93.11.5615"
    },
    {
      "key": "e_1_3_3_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(00)81050-8"
    },
    {
      "key": "e_1_3_3_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1996.tb00917.x"
    },
    {
      "key": "e_1_3_3_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/emboj/17.23.6932"
    },
    {
      "key": "e_1_3_3_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.279.5350.509"
    },
    {
      "key": "e_1_3_3_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.94.26.14671"
    },
    {
      "key": "e_1_3_3_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0960-9822(98)00015-3"
    },
    {
      "key": "e_1_3_3_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.273.10.5765"
    },
    {
      "key": "e_1_3_3_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/bbrc.1997.8064"
    },
    {
      "key": "e_1_3_3_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/34208"
    },
    {
      "key": "e_1_3_3_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1182/blood.V90.8.3089"
    },
    {
      "key": "e_1_3_3_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.91.10.4263"
    },
    {
      "key": "e_1_3_3_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(92)90163-7"
    },
    {
      "key": "e_1_3_3_24_2",
      "doi-asserted-by": "crossref",
      "first-page": "5070",
      "DOI": "10.4049/jimmunol.157.11.5070",
      "volume": "157",
      "author": "Aepfelbacher M",
      "year": "1996",
      "unstructured": "M Aepfelbacher, M Essler, E Huber, A Czech, P C Weber J Immunol 157, 5070\u20135075 (1996).",
      "journal-title": "J Immunol"
    },
    {
      "key": "e_1_3_3_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1172/JCI118712"
    },
    {
      "key": "e_1_3_3_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0014-4827(85)80044-6"
    },
    {
      "key": "e_1_3_3_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/MCB.15.10.5725"
    },
    {
      "key": "e_1_3_3_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0021-9258(18)54786-4"
    },
    {
      "key": "e_1_3_3_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1242/jcs.109.2.367"
    },
    {
      "key": "e_1_3_3_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.104.6.1521"
    },
    {
      "key": "e_1_3_3_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/8756-3282(90)90082-A"
    },
    {
      "key": "e_1_3_3_32_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0014-4827(87)90238-2"
    },
    {
      "key": "e_1_3_3_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/cm.970300405"
    },
    {
      "key": "e_1_3_3_34_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1242/jcs.104.2.595"
    },
    {
      "key": "e_1_3_3_35_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.98.4.1546"
    },
    {
      "key": "e_1_3_3_36_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/emboj/18.3.501"
    },
    {
      "key": "e_1_3_3_37_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0167-5699(98)01350-4"
    },
    {
      "key": "e_1_3_3_38_2",
      "first-page": "2981",
      "volume": "13",
      "author": "Schuuring E",
      "year": "1993",
      "unstructured": "E Schuuring, E Verhoeven, S Litvinov, R J Michalides Mol Cell Biol 13, 2981\u20132898 (1993).",
      "journal-title": "Mol Cell Biol"
    }
  ],
  "container-title": "Proceedings of the National Academy of Sciences",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://pnas.org/doi/pdf/10.1073/pnas.96.17.9648",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        4,
        22
      ]
    ],
    "date-time": "2023-04-22T12:09:02Z",
    "timestamp": 1682165342000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://pnas.org/doi/full/10.1073/pnas.96.17.9648"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1999,
        8,
        17
      ]
    ]
  },
  "references-count": 38,
  "journal-issue": {
    "issue": "17",
    "published-print": {
      "date-parts": [
        [
          1999,
          8,
          17
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1073/pnas.96.17.9648"
  ],
  "URL": "http://dx.doi.org/10.1073/pnas.96.17.9648",
  "relation": {},
  "ISSN": [
    "0027-8424",
    "1091-6490"
  ],
  "subject": [],
  "container-title-short": "Proc. Natl. Acad. Sci. U.S.A.",
  "published": {
    "date-parts": [
      [
        1999,
        8,
        17
      ]
    ]
  },
  "assertion": [
    {
      "value": "1999-04-26",
      "order": 0,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "1999-06-22",
      "order": 1,
      "name": "accepted",
      "label": "Accepted",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "1999-08-17",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}