Skap2 is required for β2 integrin–mediated neutrophil recruitment and functions

• DOI: 10.1084/jem.20160647
• Publication Date: 2017-02-09T15:20:18Z
• Authors: Mark Boras; Stephanie Volmering; Arne Bokemeyer; Jan Rossaint; Helena Block; Bernadette Bardel; Veerle Van Marck; Barbara Heitplatz; Stefanie Kliche; Annegret Reinhold; Clifford Lowell; Alexander Zarbock
• Keywords: Talin; 572; Neutrophils; 1.1 Normal biological development and functioning; Immunology; Macrophage-1 Antigen; Inbred C57BL; Medical and Health Sciences; src Homology Domains; Mice; 03 medical and health sciences; Underpinning research; Cell Adhesion; 2.1 Biological and endogenous factors; Animals; Aetiology; Research Articles; 0303 health sciences; Inflammatory and immune system; Chemotaxis; Intracellular Signaling Peptides and Proteins; Leukocyte; 3. Good health; Mice, Inbred C57BL; Chemotaxis, Leukocyte; Cytoskeletal Proteins; Neutrophil Infiltration; CD18 Antigens; Protein Multimerization; E-Selectin; Wiskott-Aldrich Syndrome Protein

Integrin activation is required for neutrophil functions. Impaired integrin on neutrophils the hallmark of leukocyte adhesion deficiency (LAD) syndrome in humans, characterized by impaired recruitment and recurrent infections. The Src kinase–associated phosphoprotein 2 (Skap2) involved functions different subtypes. However, role Skap2 β2 unknown. In this study, we demonstrate crucial regulating actin polymerization binding talin-1 kindlin-3 to cytoplasmic domain, thereby being indispensable recruitment. direct interaction with Wiskott–Aldrich protein via its SH3 domain critical vivo. Furthermore, regulates integrin-mediated outside-in signaling events Thus, essential activate integrins, loss function sufficient cause a LAD-like phenotype mice.