title: WIP: more than a WASp-interacting protein.
abstract: WIP plays an important role in the remodeling of the actin cytoskeleton, which controls cellular activation, proliferation, and function. WIP regulates actin polymerization by linking the actin machinery to signaling cascades. WIP binding to WASp and to its homolog, N-WASp, which are central activators of the actin-nucleating complex Arp2/3, regulates their cellular distribution, function, and stability. By binding to WASp, WIP protects it from degradation and thus, is crucial for WASp retention. Indeed, most mutations that result in WAS, an X-linked immunodeficiency caused by defective/absent WASp activity, are located in the WIP-binding region of WASp. In addition, by binding directly to actin, WIP promotes the formation and stabilization of actin filaments. WASp-independent activities of WIP constitute a new research frontier and are discussed extensively in this article. Here, we review the current information on WIP in human and mouse systems, focusing on its associated proteins, its molecular-regulatory mechanisms, and its role as a key regulator of actin-based processes in the immune system.
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Sophia
authors.initials: S
authors.lastname: Fried
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Omri
authors.initials: O
authors.lastname: Matalon
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Elad
authors.initials: E
authors.lastname: Noy
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel Mira.Barda-Saad@biu.ac.il.
authors.forename: Mira
authors.initials: M
authors.lastname: Barda-Saad
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D054992:Immunological Synapses / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D051300:Wiskott-Aldrich Syndrome Protein Family; D011493:Protein Kinase C
keywords: actin polymerization; cytoskeleton; immune cells; immune synapse; lymphocytes