Dedicator of cytokinesis 8 interacts with talin and Wiskott-Aldrich syndrome protein to regulate NK cell cytotoxicity

Hyoungjun Ham, Sabrice Guerrier, Jung Jin Kim, Renee A. Schoon, Erik L. Anderson, Michael J. Hamann, Zhenkun Lou, Daniel D Billadeau

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Recently, patients with mutations in DOCK8 have been reported to have a combined immunodeficiency characterized by cutaneous viral infections and allergies. NK cells represent a first-line defense against viral infections, suggesting that DOCK8 might participate in NK cell function. In this study, we demonstrate that DOCK8-suppressed human NK cells showed defects in natural cytotoxicity as well as specific activating receptor-mediated NK cytotoxicity. Additionally, compared with control NK cells, NK cells depleted of DOCK8 showed defective conjugate formation, along with decreased polarization of LFA-1, F-actin, and cytolytic granules toward the cytotoxic synapse. Using a proteomic approach, we found that DOCK8 exists in a macromolecular complex with the Wiskott-Aldrich syndrome protein, an actin nucleation-promoting factor activated by CDC42, as well as talin, which is required for integrin-mediated adhesion. Taken together, our results demonstrate an important role for DOCK8 in NK cell effector function and provide important new mechanistic insight into how DOCK8 regulates F-actin and integrin-mediated adhesion in immune cells.

Original languageEnglish (US)
Pages (from-to)3661-3669
Number of pages9
JournalJournal of Immunology
Volume190
Issue number7
DOIs
StatePublished - Apr 1 2013

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Wiskott-Aldrich Syndrome Protein
Talin
Cytokinesis
Natural Killer Cells
Actins
Virus Diseases
Integrins
Macromolecular Substances
Lymphocyte Function-Associated Antigen-1
Proteomics
Synapses
Hypersensitivity
Skin
Mutation

ASJC Scopus subject areas

  • Immunology

Cite this

Dedicator of cytokinesis 8 interacts with talin and Wiskott-Aldrich syndrome protein to regulate NK cell cytotoxicity. / Ham, Hyoungjun; Guerrier, Sabrice; Kim, Jung Jin; Schoon, Renee A.; Anderson, Erik L.; Hamann, Michael J.; Lou, Zhenkun; Billadeau, Daniel D.

In: Journal of Immunology, Vol. 190, No. 7, 01.04.2013, p. 3661-3669.

Research output: Contribution to journalArticle

Ham, Hyoungjun ; Guerrier, Sabrice ; Kim, Jung Jin ; Schoon, Renee A. ; Anderson, Erik L. ; Hamann, Michael J. ; Lou, Zhenkun ; Billadeau, Daniel D. / Dedicator of cytokinesis 8 interacts with talin and Wiskott-Aldrich syndrome protein to regulate NK cell cytotoxicity. In: Journal of Immunology. 2013 ; Vol. 190, No. 7. pp. 3661-3669.
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AU - Anderson, Erik L.

AU - Hamann, Michael J.

AU - Lou, Zhenkun

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