Abi is required for modulation and stability but not localization or activation of the SCAR/WAVE complex

Davidson, A.J., Ura, S., Thomason, P.A., Kalna, G. and Insall, R.H. (2013) Abi is required for modulation and stability but not localization or activation of the SCAR/WAVE complex. Eukaryotic Cell, 12(11), pp. 1509-1516. (doi: 10.1128/EC.00116-13) (PMID:24036345) (PMCID:PMC3837927)

Abstract

The SCAR/WAVE complex drives actin-based protrusion, cell migration, and cell separation during cytokinesis. However, the contribution of the individual complex members to the activity of the whole remains a mystery. This is primarily because complex members depend on one another for stability, which limits the scope for experimental manipulation. Several studies suggest that Abi, a relatively small complex member, connects signaling to SCAR/WAVE complex localization and activation through its polyproline C-terminal tail. We generated a deletion series of the Dictyostelium discoideum Abi to investigate its exact role in regulation of the SCAR complex and identified a minimal fragment that would stabilize the complex. Surprisingly, loss of either the N terminus of Abi or the C-terminal polyproline tail conferred no detectable defect in complex recruitment to the leading edge or the formation of pseudopods. A fragment containing approximately 20% Abi—and none of the sites that couple to known signaling pathways—allowed the SCAR complex to function with normal localization and kinetics. However, expression of N-terminal Abi deletions exacerbated the cytokinesis defect of the Dictyostelium abi mutant, which was earlier shown to be caused by the inappropriate activation of SCAR. This demonstrates, unexpectedly, that Abi does not mediate the SCAR complex's ability to make pseudopods, beyond its role in complex stability. Instead, we propose that Abi has a modulatory role when the SCAR complex is activated through other mechanisms.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Ura, Mr Seiji and Thomason, Dr Peter and Davidson, Mr Andrew and Insall, Professor Robert and Kalna, Dr Gabriela
• Authors: Davidson, A.J., Ura, S., Thomason, P.A., Kalna, G., and Insall, R.H.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Eukaryotic Cell
• ISSN: 1535-9778
• ISSN (Online): 1535-9786