Disease relevance of WASp

• Here, we report that the Wiskott-Aldrich syndrome protein (WASp) is necessary for rhabdomere microvillus morphogenesis [1].

High impact information on WASp

• Nervous wreck, an SH3 adaptor protein that interacts with Wsp, regulates synaptic growth in Drosophila [2].
• WASp is required for the correct temporal morphogenesis of rhabdomere microvilli [1].
• The loss of WASp delays the enrichment of F-actin on the apical photoreceptor surface, delays the appearance of the primordial microvillar projections, and subsequently leads to malformed rhabdomeres [1].
• The nature of the Wsp mutant phenotypes, coupled with genetic interaction studies, identifies an essential role for Wsp in lineage decisions mediated by the Notch signaling pathway [3].
• The requirement for Wsp extends to additional cell fate decisions in lineages of the embryonic central nervous system and mesoderm [3].

Biological context of WASp

• Finally, RNA interference studies in S2 cells indicated that the D-SCAR homolog D-WASp also participates in phagocytosis [4].
• By contrast, depletion of WASp did not produce any significant phenotype, except for a slight inhibition of spreading, showing that both lamellipodia and filopodia in Drosophila cells are regulated predominantly by SCAR [5].
• Phenotypic analysis of Wsp mutant animals demonstrates a bias towards neuronal differentiation, at the expense of other cell types, resulting from improper execution of the program of asymmetric cell divisions which underlie sensory organ development [3].

Anatomical context of WASp

• We performed targeted depletion of SCAR or WASp by dsRNA-mediated interference in two Drosophila cultured cell lines expressing lamellipodial and filopodial protrusion [5].
• Furthermore, we could show that both proteins stabilize each other and directly control the regulation of the F-actin cytoskeleton in a Wasp-dependent manner [6].

Associations of WASp with chemical compounds

• 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 [7].

Regulatory relationships of WASp

• This gain-of-function phenotype is independent of wave but can be suppressed by reducing the wasp gene dose, indicating that Kette is able to regulate Wasp, to which it is linked via the Abelson interactor (Abi) [8].

Other interactions of WASp

• Sra-1 interacts with Kette and Wasp and is required for neuronal and bristle development in Drosophila [6].
• An important regulator of F-actin formation is the Arp2/3 complex, which in turn is activated by Wasp and Wave [6].

References