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WIP Remodeling Actin behind the Scenes: How WIP Reshapes Immune and Other Functions
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 16 May 2012; in revised form: 7 June 2012 / Accepted: 14 June 2012 / Published: 21 June 2012
Abstract: Actin polymerization is a fundamental cellular process regulating immune cell functions and the immune response. The Wiskott-Aldrich syndrome protein (WASp) is an actin nucleation promoting factor, which is exclusively expressed in hematopoietic cells, where it plays a key regulatory role in cytoskeletal dynamics. WASp interacting protein (WIP) was first discovered as the binding partner of WASp, through the use of the yeast two hybrid system. WIP was later identified as a chaperone of WASp, necessary for its stability. Mutations occurring at the WASp homology 1 domain (WH1), which serves as the WIP binding site, were found to cause the Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT). WAS manifests as an immune deficiency characterized by eczema, thrombocytopenia, recurrent infections, and hematopoietic malignancies, demonstrating the importance of WIP for WASp complex formation and for a proper immune response. WIP deficiency was found to lead to different abnormalities in the activity of various lymphocytes, suggesting differential cell-dependent roles for WIP. Additionally, WIP deficiency causes cellular abnormalities not found in WASp-deficient cells, indicating that WIP fulfills roles beyond stabilizing WASp. Indeed, WIP was shown to interact with various binding partners, including the signaling proteins Nck, CrkL and cortactin. Recent studies have demonstrated that WIP also takes part in non immune cellular processes such as cancer invasion and metastasis, in addition to cell subversion by intracellular pathogens. Understanding of numerous functions of WIP can enhance our current understanding of activation and function of immune and other cell types.
Keywords: WIP; WASp; actin; cytoskeleton; immune response; lymphocytes; TCR signaling
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Noy, E.; Fried, S.; Matalon, O.; Barda-Saad, M. WIP Remodeling Actin behind the Scenes: How WIP Reshapes Immune and Other Functions. Int. J. Mol. Sci. 2012, 13, 7629-7647.
Noy E, Fried S, Matalon O, Barda-Saad M. WIP Remodeling Actin behind the Scenes: How WIP Reshapes Immune and Other Functions. International Journal of Molecular Sciences. 2012; 13(6):7629-7647.
Noy, Elad; Fried, Sophia; Matalon, Omri; Barda-Saad, Mira. 2012. "WIP Remodeling Actin behind the Scenes: How WIP Reshapes Immune and Other Functions." Int. J. Mol. Sci. 13, no. 6: 7629-7647.