Disease relevance of Wasf1

• Scar/WAVE-1, a Wiskott-Aldrich syndrome protein, assembles an actin-associated multi-kinase scaffold [1].
• Malignant B16F10 mouse melanoma cells expressed more WAVE1 and WAVE2 proteins and showed higher Rac activity than B16 parental cells, which are neither invasive nor metastatic [2].

Psychiatry related information on Wasf1

• These sensorimotor and cognitive deficits are analogous to the symptoms of patients with 3p-syndrome mental retardation who are haploinsufficient for WRP/MEGAP, a component of the WAVE-1 signaling network [3].

High impact information on Wasf1

• Immunocytochemical analyses in Swiss 3T3 fibroblasts suggest that the WAVE-1 kinase scaffold is assembled dynamically as WAVE, PKA and Abl translocate to sites of actin reorganization in response to platelet-derived growth factor treatment [1].
• The Scar/WAVE family of scaffolding proteins organize molecular networks that relay signals from the GTPase Rac to the actin cytoskeleton [3].
• The WAVE-1 isoform is a brain-specific protein expressed in variety of areas including the regions of the hippocampus and the Purkinje cells of the cerebellum [3].
• Although the VCA domain imbues WASp and other WASp family members with the capacity to modulate cytoskeletal organization, little is known about the impact of this domain activity on lymphoid cell function [4].
• Thus, Abi-1 undergoes nucleocytoplasmic shuttling and functions at the leading edge to regulate Wave-1 localization and protein levels [5].

Biological context of Wasf1

• We finally show that the genomic structure is highly conserved among these genes and that the mouse Wave genes map to chromosome regions that have synteny in the human genome [6].
• Downregulation of Abi expression by RNA interference impaired adherens junction formation and correlated with downregulation of the Wave actin-nucleation promoting factor [7].
• The Wave1 transcription initiation site was mapped 210 base pairs upstream of the ATG translational start site [8].
• The mouse Wave1 gene was physically localized on chromosome 10 and spans over 12 Kb comprising eight exons and seven introns [8].
• To evaluate the role of WASP/WAVE proteins in the process of neuronal morphogenesis, we used a retroviral gene trap to generate a line of mice bearing a disruption in the WAVE1 gene [9].

Anatomical context of Wasf1

• Mouse embryo fibroblasts that lack one allele of Abi-1 and are homozygous null for the related Abi-2 protein exhibit decreased Wave-1 protein levels [5].
• Arp2/3 complex is believed to induce de novo nucleation of actin filaments at the edge of motile cells downstream of WASp family proteins [10].
• A novel function of WAVE in lamellipodia: WAVE1 is required for stabilization of lamellipodial protrusions during cell spreading [11].
• Northern analysis demonstrated a strong expression of a unique approximately 2.6 Kb Wave1 transcript in brain tissue, and in situ hybridization showed restricted expression to Purkinje cells from the cerebellum and pyramidal cells from the hippocampus [8].
• RESULTS: Here we show that Abi and Wave rapidly translocate from the T cell cytoplasm to the T cell:B cell contact site in the presence of antigen [12].

Associations of Wasf1 with chemical compounds

• The mouse Wave1 complementary DNA encodes a predicted 559 amino acid protein, with a SCAR homology domain, a basic domain, a proline-rich region, a WASP homology domain and an acidic domain conserved in the orthologous proteins [8].
• The localisation of Scar was facilitated by the finding that the formerly described inhibition of lamellipodia formation by ectopical expression of Scar, could be overcome by the treatment of cells with aluminium fluoride [13].
• In the pretest nimodipine significantly increased the latency of Wave P1 of the ABR (mean difference: 0.16 ms; P < 0.02), showing that calcium blockade depressed sensorineural efficiency, but ABR thresholds were not affected [14].
• Difficulty in growing cholesterol-dependent NS0 cells in the Wave bioreactor using the original low-density polypropylene (LDPE) bags has been encountered [15].
• Cyclic AMP (cAMP) signalling reduces phosphorylation of the Cdk5 sites in WAVE1, and increases spine density in a WAVE1-dependent manner [16].

Enzymatic interactions of Wasf1

• Here we show that WAVE1 is phosphorylated at multiple sites by cyclin-dependent kinase 5 (Cdk5) both in vitro and in intact mouse neurons [16].

Other interactions of Wasf1

• The effect of WAVE2 silencing by RNA interference (RNAi) on the highly invasive nature of B16F10 cells was more dramatic than that of WAVE1 RNAi [2].
• Gene targeting experiments in mice demonstrate that WRP anchoring to WAVE-1 is a homeostatic mechanism that contributes to neuronal development and the fidelity of synaptic connectivity [17].
• Next, we found WAVE1, WAVE2 and WAVE3 [18].
• WAVE1 has been reported to associate and activate Arp2/3 complex at its C-terminal region that is rich in acidic residues [19].
• Phosphorylation of WAVE1 by Cdk5 inhibits its ability to regulate Arp2/3 complex-dependent actin polymerization [16].

References