Conserved interactions with cytoskeletal but not signaling elements are an essential aspect of Drosophila WASp function.

Wiskott-Aldrich Syndrome proteins (WASp) serve as important regulators of cytoskeletal organization and function. These modular proteins, which are well-conserved among eukaryotic species, act to promote actin filament assembly in response to cues from various signal transduction pathways. Genetic analysis has revealed a requirement for the single Drosophila homolog, Wasp (Wsp), in cell-fate decisions governing specific neuronal lineages. We have used this unique developmental context to assess the contributions of established signaling and cytoskeletal partners of WASp. We present biochemical and genetic evidence that, as expected, Drosophila Wsp performs its developmental role via the Arp2/3 complex, indicating conservation of the cytoskeletal aspect of Wsp function in vivo. In contrast, we find that association with the key signaling molecules CDC42 and PIP2 is not an essential requirement, implying that activation of Wsp function in vivo depends on additional or alternative signaling pathways.

Tal T ，Vaizel-Ohayon D ，Schejter ED 《DEVELOPMENTAL BIOLOGY》

A conserved amphipathic helix in WASP/Scar proteins is essential for activation of Arp2/3 complex.

Panchal SC ，Kaiser DA ，Torres E ，Pollard TD ，Rosen MK ... -  《-》

Wiskott-Aldrich syndrome: a disorder of haematopoietic cytoskeletal regulation.

The Wiskott-Aldrich Syndrome (WAS) is a rare inherited X-linked recessive disease characterised by immune dysregulation and microthrombocytopenia. Recently, the biological mechanisms that are responsible for the pathophysiology of WAS have been shown to be linked to the regulation of the actin cytoskeleton in haematopoietic cells. The WAS protein (WASp) is now known to be a member of a unique family that share similar domain structures, and that are responsible for transduction of signals from the cell membrane to the actin cytoskeleton. The interactions between WASp, the Rho family GTPase Cdc42, and the cytoskeletal organising complex Arp2/3 are probably critical to many of these functions, which, when disturbed, translate into measurable defects of cell polarisation and motility.

Thrasher AJ ，Burns S 《MICROSCOPY RESEARCH AND TECHNIQUE》

Differential regulation of WASP and N-WASP by Cdc42, Rac1, Nck, and PI(4,5)P2.

Tomasevic N ，Jia Z ，Russell A ，Fujii T ，Hartman JJ ，Clancy S ，Wang M ，Beraud C ，Wood KW ，Sakowicz R ... -  《BIOCHEMISTRY》

WASp in immune-system organization and function.

Thrasher AJ 《NATURE REVIEWS IMMUNOLOGY》