Direction of leukocyte polarization and migration by the phosphoinositide-transfer protein TIPE2 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Svetlana A Fayngerts, Zhaojun Wang, Ali Zamani, Honghong Sun, Amanda E Boggs, Thomas P Porturas, Weidong Xie, Mei Lin, Terry Cathopoulis, Jason R Goldsmith, Anastassios Vourekas, Youhai H Chen

ABSTRACT

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. More... »

PAGES

1353-1360

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ni.3866

    DOI

    http://dx.doi.org/10.1038/ni.3866

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1092346889

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29058702


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