The migration of cells and the movement of some intracellular pathogens, such as Shigella and Vaccinia, are dependent on the actin-based cytoskeleton.
Many proteins are involved in regulating the dynamics of the actin-based microfilaments within cells and, among them, WASP and N-WASP have a significant role in the regulation of actin polymerisation.
The activity and stability of WASP is regulated by its cellular partner WASP-interacting protein (WIP) during the formation of actin-rich structures, including the immune synapse, filopodia, lamellipodia, stress fibres and podosomes.
The actin cytoskeleton plays critical roles in cell morphologic changes and motility. Rho family small GTPases, such as Rho (MIM.165370), RAC (MIM.602048), and CDC42 (MIM.116952), organize the actin cytoskeleton.
Other major players in actin-based motility are the 7 members of the ARP2/3 complex (MIM.604221).
The Wiskott-Aldrich syndrome protein (WASP) (MIM.301000), WASP-like (WASL) (MIM.605056), and WASF1 are among the downstream effector molecules involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton.
WASP-WAVE network
Wiskott-Aldrich syndrome protein (WASP) and WASP-family verprolin-homologous protein (WAVE or WASF1) family proteins are scaffolds that link upstream signals to the activation of the ARP2/3 complex, leading to a burst of actin polymerization.
ARP2/3-complex-mediated actin polymerization is crucial for the reorganization of the actin cytoskeleton at the cell cortex for processes such as cell movement, vesicular trafficking and pathogen infection.
Large families of membrane-binding proteins interact with WASP and WAVE family proteins, therefore providing a new layer of membrane-dependent regulation of actin polymerization.
Pathology
germ-lime mutations in Wiskott-Aldrich syndrome
germ-line mutations in the X-linked thrombocytopenia (XLT)
See also
WASP-family members
WIPFs (WIPF1, WIPF2)
Arp2/3
lamellipodia
WAS (WASP)
WASL
References
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Takenawa T, Suetsugu S. The WASP-WAVE protein network: connecting the membrane to the cytoskeleton. Nat Rev Mol Cell Biol. 2007 Jan;8(1):37-48. PMID: 17183359
Notarangelo LD, Notarangelo LD, Ochs HD. WASP and the phenotypic range associated with deficiency. Curr Opin Allergy Clin Immunol. 2005 Dec;5(6):485-90. PMID: 16264326
Stradal TE, Rottner K, Disanza A, Confalonieri S, Innocenti M, Scita G. Regulation of actin dynamics by WASP and WAVE family proteins. Trends Cell Biol. 2004 Jun;14(6):303-11. PMID: 15183187
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Imai K, Nonoyama S, Ochs HD. WASP (Wiskott-Aldrich syndrome protein) gene mutations and phenotype. Curr Opin Allergy Clin Immunol. 2003 Dec;3(6):427-36. PMID: 14612666
Snapper SB, Rosen FS: The Wiskott-Aldrich syndrome protein (WASP): roles in signaling and cytoskeletal organization. Annu Rev Immunol 17:905, 1999.