Wiskott-Aldrich Syndrome Protein Regulates Podosomes in Primary Human Macrophages

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1999 Aug 18

PMID 10449748

Citations 158

Authors

S Linder

D Nelson

M Weiss

M Aepfelbacher

Affiliations

Soon will be listed here.

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.

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References

Dutartre H, Davoust J, Gorvel J, Chavrier P . Cytokinesis arrest and redistribution of actin-cytoskeleton regulatory components in cells expressing the Rho GTPase CDC42Hs. J Cell Sci. 1996; 109 ( Pt 2):367-77. DOI: 10.1242/jcs.109.2.367. View

Kenney D, Cairns L, Remold-ODonnell E, Peterson J, Rosen F, Parkman R . Morphological abnormalities in the lymphocytes of patients with the Wiskott-Aldrich syndrome. Blood. 1986; 68(6):1329-32. View

Ridley A, Hall A . The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell. 1992; 70(3):389-99. DOI: 10.1016/0092-8674(92)90163-7. View

Hart M, Shinjo K, Hall A, Evans T, Cerione R . Identification of the human platelet GTPase activating protein for the CDC42Hs protein. J Biol Chem. 1991; 266(31):20840-8. View

Sanchez-Madrid F, Del Pozo M . Leukocyte polarization in cell migration and immune interactions. EMBO J. 1999; 18(3):501-11. PMC: 1171143. DOI: 10.1093/emboj/18.3.501. View

Kirchhausen T . Wiskott-Aldrich syndrome: a gene, a multifunctional protein and the beginnings of an explanation. Mol Med Today. 1998; 4(7):300-4. DOI: 10.1016/s1357-4310(98)01268-4. View

Hall A . Rho GTPases and the actin cytoskeleton. Science. 1998; 279(5350):509-14. DOI: 10.1126/science.279.5350.509. View

Aepfelbacher M, Vauti F, Weber P, Glomset J . Spreading of differentiating human monocytes is associated with a major increase in membrane-bound CDC42. Proc Natl Acad Sci U S A. 1994; 91(10):4263-7. PMC: 43765. DOI: 10.1073/pnas.91.10.4263. View

Ramesh N, Anton I, Hartwig J, Geha R . WIP, a protein associated with wiskott-aldrich syndrome protein, induces actin polymerization and redistribution in lymphoid cells. Proc Natl Acad Sci U S A. 1998; 94(26):14671-6. PMC: 25088. DOI: 10.1073/pnas.94.26.14671. View

10.

Schindelhauer D, Weiss M, Hellebrand H, Golla A, Hergersberg M, Seger R . Wiskott-Aldrich syndrome: no strict genotype-phenotype correlations but clustering of missense mutations in the amino-terminal part of the WASP gene product. Hum Genet. 1996; 98(1):68-76. DOI: 10.1007/s004390050162. View

11.

Marchisio P, Cirillo D, Teti A, Tarone G . Rous sarcoma virus-transformed fibroblasts and cells of monocytic origin display a peculiar dot-like organization of cytoskeletal proteins involved in microfilament-membrane interactions. Exp Cell Res. 1987; 169(1):202-14. DOI: 10.1016/0014-4827(87)90238-2. View

12.

Aepfelbacher M, Essler M, Huber E, Czech A, Weber P . Rho is a negative regulator of human monocyte spreading. J Immunol. 1996; 157(11):5070-5. View

13.

Thrasher A, Jones G, Kinnon C, Brickell P, Katz D . Is Wiskott--Aldrich syndrome a cell trafficking disorder?. Immunol Today. 1998; 19(12):537-9. DOI: 10.1016/s0167-5699(98)01350-4. View

14.

Rivero-Lezcano O, Marcilla A, Sameshima J, ROBBINS K . Wiskott-Aldrich syndrome protein physically associates with Nck through Src homology 3 domains. Mol Cell Biol. 1995; 15(10):5725-31. PMC: 230823. DOI: 10.1128/MCB.15.10.5725. View

15.

Kanehisa J, Yamanaka T, Doi S, Turksen K, Heersche J, Aubin J . A band of F-actin containing podosomes is involved in bone resorption by osteoclasts. Bone. 1990; 11(4):287-93. DOI: 10.1016/8756-3282(90)90082-a. View

16.

Binks M, Jones G, Brickell P, Kinnon C, Katz D, Thrasher A . Intrinsic dendritic cell abnormalities in Wiskott-Aldrich syndrome. Eur J Immunol. 1998; 28(10):3259-67. DOI: 10.1002/(SICI)1521-4141(199810)28:10<3259::AID-IMMU3259>3.0.CO;2-B. View

17.

Schuuring E, Verhoeven E, Litvinov S, Michalides R . The product of the EMS1 gene, amplified and overexpressed in human carcinomas, is homologous to a v-src substrate and is located in cell-substratum contact sites. Mol Cell Biol. 1993; 13(5):2891-98. PMC: 359682. DOI: 10.1128/mcb.13.5.2891-2898.1993. View

18.

Aspenstrom P, Lindberg U, Hall A . Two GTPases, Cdc42 and Rac, bind directly to a protein implicated in the immunodeficiency disorder Wiskott-Aldrich syndrome. Curr Biol. 1996; 6(1):70-5. DOI: 10.1016/s0960-9822(02)00423-2. View

19.

Stewart D, Treiber-Held S, Kurman C, Facchetti F, Notarangelo L, Nelson D . Studies of the expression of the Wiskott-Aldrich syndrome protein. J Clin Invest. 1996; 97(11):2627-34. PMC: 507350. DOI: 10.1172/JCI118712. View

20.

Remold-ODonnell E, Rosen F, Kenney D . Defects in Wiskott-Aldrich syndrome blood cells. Blood. 1996; 87(7):2621-31. View