β1 integrins regulate fibroblast chemotaxis through control of N-WASP stability

King, Samantha J., et al. 2011. EMBO. J. 30, 1705–1718.

Speaker: Yu-Zhen Lu (呂瑜珍)                                     Time: 14:00~14:50, Nov. 30, 2011

Commentator: Dr. Hsiao-Sheng Liu (劉校生博士)      Place: Room 601

Abstract

Integrins are cell surface receptors known for their interaction with extracellular matrix  proteins. Through matrix proteins binding, integrin transduces signals for proliferation, differentiation, and migration¹. Recent studies showed that integrins can also cooperate with several growth factor receptors to promote optimal downstream signaling, like epidermal growth factor receptor and platelet-derived growth factor (PDGF) receptor. The signaling mechanisms which regulate this crosstalk are still poorly understood. In this study, the authors investigated how β1 integrin regulates PDGFR signaling during chemotaxis. By using β1 floxed mice to generate β1+/+ (not cre treated) fibroblast, β1 null fibroblast (β1-/- cre recombinase treated) or β1-/- fibroblast rescued with human β1 tagged with GFP (β1-GFP), the authors found that β1 integrin can promote fibroblastchemotaxis towards PDGF and ruffle dorsal formation through stabilizing the neuronal Wiskott-Aldrilch syndrome protein (N-WASP)². N-WASP is key effector regulating dynamic changes in the actin cytoskeleton and cell migration. Mutations in the Wiskott-Aldrilch syndrome gene leads to severe immunodeficiency disease. Upon PDGF stimulation, β1 integrin will be activated to regulate the N-WASP- WIP (WASP-interacting protein) complex formation. Besides, active β1 integrin can also promote Cdc42 activation and the assembly of Cdc42 and N-WASP. These protein complexes are important for PDGF recrptor internalisation and fibroblast chemotaxis. This study provides novel insight into the assembly of these signaling protein complexes in migrating fibroblast.

References:

1          Streuli, Charles H. and Akhtar, N. 2009. Signal co-operation between integrins and other receptor systems. Biochem. J. 418, 491-506.

2          Kurisu, S. and Takenawa, T. 2009.The WASP and WAVE family proteins. Genome Biol. 10, 226-233.