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Direction of leukocyte polarization and migration by the phosphoinositide-transfer protein TIPE2
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Direction of leukocyte polarization and migration by the phosphoinositide-transfer protein TIPE2
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Journal Article
Direction of leukocyte polarization and migration by the phosphoinositide-transfer protein TIPE2
2017
Overview
The polarization of leukocytes toward chemoattractants is essential for their directed migration. Chen and colleagues show that the phosphoinositide-transfer protein TIPE2 functions as a coordinator of leukocyte polarity.
The polarization of leukocytes toward chemoattractants is essential for the directed migration (chemotaxis) of leukocytes. How leukocytes acquire polarity after encountering chemical gradients is not well understood. We found here that leukocyte polarity was generated by TIPE2 (TNFAIP8L2), a transfer protein for phosphoinositide second messengers. TIPE2 functioned as a local enhancer of phosphoinositide-dependent signaling and cytoskeleton remodeling, which promoted leading-edge formation. Conversely, TIPE2 acted as an inhibitor of the GTPase Rac, which promoted trailing-edge polarization. Consequently, TIPE2-deficient leukocytes were defective in polarization and chemotaxis, and TIPE2-deficient mice were resistant to leukocyte-mediated neural inflammation. Thus, the leukocyte polarizer is a dual-role phosphoinositide-transfer protein and represents a potential therapeutic target for the treatment of inflammatory diseases.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 64/60
/ 96/21
/ Animals
/ Chemotaxis, Leukocyte - genetics
/ Chemotaxis, Leukocyte - physiology
/ Encephalomyelitis, Autoimmune, Experimental - immunology
/ Intracellular Signaling Peptides and Proteins - genetics
/ Mice
/ Phosphatidylinositol phosphates
/ Phosphatidylinositols - metabolism
/ Phosphotransferases (Alcohol Group Acceptor) - metabolism
/ Polarity
/ Proteins
/ rac GTP-Binding Proteins - antagonists & inhibitors
/ Signal Transduction - genetics
