Disease relevance of Wasl

• Neuronal Wiskott-Aldrich Syndrome protein (N-WASP) transmits signals from Cdc42 to the nucleation of actin filaments by Arp2/3 complex [1].

High impact information on Wasl

• N-WASP, a ubiquitously expressed Cdc42-interacting protein, is required for Cdc42-stimulated actin polymerization in Xenopus egg extracts [2].
• Therefore, N-WASP and the Arp2/3 complex comprise a core mechanism that directly connects signal transduction pathways to the stimulation of actin polymerization [2].
• Phosphatidylinositol 4,5-bisphosphate (PIP(2)) activates the actin regulatory protein N-WASP by binding to a short polybasic region involved in N-WASP autoinhibition [3].
• Molecular mechanisms of invadopodium formation: the role of the N-WASP-Arp2/3 complex pathway and cofilin [4].
• Depletion of endogenous N-WASP by sequestering it to mitochondria or by introducing anti-N-WASP antibodies impaired endocytosis [5].

Biological context of Wasl

• We dissected this activation reaction and found that the previously described physical interaction between the NH(2)-terminal domain and the COOH-terminal effector domain of N-WASP is a regulatory interaction because it can inhibit the actin nucleation activity of the effector domain by occluding the Arp2/3 binding site [1].
• Regulated exocytosis in neuroendocrine cells: a role for subplasmalemmal Cdc42/N-WASP-induced actin filaments [6].
• To detect and image sites of N-WASP activity during cell motility and invasion in carcinoma cells, we designed an N-WASP fluorescence resonance energy transfer (FRET) biosensor that distinguishes between the active and inactive conformations and mimics the function of endogenous N-WASP [7].
• We reported here the cloning and sequencing of three such ESTs: TRS1, TRS3, and TRS4 [8].

Anatomical context of Wasl

• Here we examined the possible involvement of N-WASP in the neurite extension process [9].
• Expression of Deltacof N-WASP suppressed neurite extension of PC12 cells [9].
• We have isolated cDNAs encoding Aplysia Rho, Rac, and Cdc42 and found that Rho and Rac had no effect but that overexpression in sensory neurons of a dominant-negative mutant of ApCdc42 or the CRIB domains of its downstream effectors PAK and N-WASP selectively reduces the long-term changes in synaptic strength and structure [10].
• Our results demonstrate for the first time that secretagogue-evoked stimulation induces the sequential ordering of Cdc42, N-WASP, and Arp2/3 at the interface between granules and the plasma membrane, thereby providing an actin structure that makes the exocytotic machinery more efficient [6].
• Imaging sites of N-wasp activity in lamellipodia and invadopodia of carcinoma cells [7].

Associations of Wasl with chemical compounds

• Serotonin-induced regulation of the actin network for learning-related synaptic growth requires Cdc42, N-WASP, and PAK in Aplysia sensory neurons [10].
• This interaction between the NH(2)- and COOH termini must be intramolecular because in solution N-WASP is a monomer [1].
• On one hand, a peptide fragment of neural Wiskott-Aldrich syndrome protein (N-WASP), which interacts with acidic phospholipids like aminoglycosides, inhibited gentamicin accumulation not only in OK cells but also in mouse kidney [11].

Regulatory relationships of Wasl

• Neural Wiskott-Aldrich syndrome protein (N-WASP) is an actin-regulating protein that induces filopodium formation downstream of Cdc42 [9].

Other interactions of Wasl

• Therefore, we found that functionally different splicing variants of Rapostlin have different responses to Rnd2 in association with N-WASP [12].
• Although full-length N-WASP is less effective, its activity can be greatly enhanced by Cdc42 and phosphatidylinositol (4,5) bisphosphate [2].
• Although neither neural Wiskott-Aldrich syndrome protein (N-WASP) nor WASP interacting SH3 protein (WISH) immunoreactivity was co-localized with filamentous actin (F-actin) distribution, both WASP family verprolin-homologous protein (WAVE) and Rac1 immunoreactivity was co-localized with F-actin in the lamellipodia of phogocytic microglia [13].

Analytical, diagnostic and therapeutic context of Wasl

• In immunoprecipitation experiments, Rnd2 reduces RapostlinL-N-WASP interaction, whereas it has little effect on the interaction of RapostlinM or RapostlinS with N-WASP [12].

References