Recent advances in the biology of WASP and WIP

Division of Immunology, Department of Pediatrics, Childrens Hospital, Harvard Medical School, Karp 10 One Blackfan Circle, Boston, MA, 02115, USA.
Immunologic Research (Impact Factor: 3.1). 12/2008; 44(1-3):99-111. DOI: 10.1007/s12026-008-8086-1
Source: PubMed


WASP, the product of the gene mutated in Wiskott-Aldrich syndrome, is expressed only in hematopoietic cells and is the archetype of a family of proteins that include N-WASP and Scar/WAVE. WASP plays a critical role in T cell activation and actin reorganization. WASP has multiple protein-interacting domains. Through its N-terminal EVH1 domain WASP binds to its partner WASP interacting protein (WIP) and through its C-terminal end it interacts with and activates the Arp2/3 complex. In lymphocytes, most of WASP is sequestered with WIP and binding to WIP is essential for the stability of WASP. The central proline-rich region of WASP serves as docking site to several adaptor proteins. Through these multiple interactions WASP integrates many cellular signals to actin cytoskeleton remodeling. In this review, we have summarized recent developments in the biology of WASP and the role of WIP in regulating WASP function. We also discuss WASP-independent functions of WIP.

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    • "Similar numbers of genes were significantly up- or downregulated (269 up-regulated, 225 downregulated; Figure 5(a), Table S4). Many of the upregulated transcripts are involved in regulating neurotransmission (otoferlin, Otof [41]: Wiskott-Aldrich syndrome protein interacting protein family 1, Wipf1 [42]; neurotrophin receptor tyrosine kinase 3, Ntrk3 [43]; calcium/calmodulin kinase 1D, CamK1d [44]) and differentiation YLP motif containing 1 (Ylpm1 [45]). CR in the WT animals, however, caused profound suppression of multiple energy-modulatory factors including insulin-like growth factor 1 (Igf1), phospholipid transfer protein (Pltp), and neuronal ceroid lipofuscinosis 6 (Cln6), which were significantly downregulated following CR. "
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    • "Binding to WIP not only inhibits WASp but also is necessary for its stability. Furthermore, WIP is also a chaperone of WASp, regulating its activation and is responsible for the localization of WASp at actin rearrangement site followed by T cell activation (86-88). WIP was reported to be essential for IL-2 signalling and responsiveness in T cells (89). "
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    Immune Network 06/2012; 12(3):71-83. DOI:10.4110/in.2012.12.3.71
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    • "Wiskott-Aldrich syndrome protein interacting protein (WIP) is another important regulator of the actin cytoskeleton that inhibits Cdc42-mediated activation of WASP. Most of WASP in lymphocytes appear to be sequestered with WIP, and binding to WIP is essential for the stability of WASP (Ramesh and Geha, 2009). More efficient generation of actin filaments was detected in WIP-deficient BMMCs activated by FcεRI aggregation (Kettner et al., 2004). "
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