Memo is a cofilin-interacting protein that influences PLC{gamma}1 and cofilin activities, and is essential for maintaining directionality during ErbB2-induced tumor-cell migration.
Tools
Tools
Meira, Maria, Masson, Regis, Stagljar, Igor, Lienhard, Susanne, Maurer, Francisca, Boulay, Anne and Hynes, Nancy (2009) Memo is a cofilin-interacting protein that influences PLC{gamma}1 and cofilin activities, and is essential for maintaining directionality during ErbB2-induced tumor-cell migration. Journal of Cell Science, 122 (Pt 6). pp. 787-797. ISSN 0021-9533
Abstract
Heregulin (HRG) activates ErbB2-ErbB3 heterodimers thereby stimulating many cellular responses, including motility. Memo and PLCgamma1 interact with ErbB2 autophosphorylation sites and are essential for HRG-induced chemotaxis. By tracing HRG-stimulated cell migration in Dunn chambers, we found that Memo- or PLCgamma1 knockdown (KD) strongly impairs cell directionality. Memo has no obvious enzymatic activity and was discovered via its ability to complex with ErbB2. Using the yeast two-hybrid approach to gain insight into Memo function, an interaction between Memo and cofilin, a regulator of actin dynamics, was uncovered. The interaction was confirmed in vitro using recombinant proteins and in vivo in co-immunoprecipitation experiments where Memo was detected in complexes with cofilin, ErbB2 and PLCgamma1. Interestingly, in Memo KD cells, HRG-induced PLCgamma1 phosphorylation was decreased, suggesting that Memo regulates PLCgamma1 activation. Furthermore, HRG-induced recruitment of GFP-cofilin to lamellipodia is impaired in Memo and in PLCgamma1 KD cells, suggesting that both proteins lie upstream of cofilin in models of ErbB2-driven tumor-cell migration. Finally, in vitro F-actin binding and depolymerization assays showed that Memo enhances cofilin depolymerizing and severing activity. In summary, these data indicate that Memo also regulates actin dynamics by interacting with cofilin and enhancing its function.
| Item Type: | Article |
|---|---|
| Related URLs: | |
| Additional Information: | author can archive post-print (ie final draft post-refereeing); On author's personal web site; Publisher's version/PDF may be used |
| Keywords: | Heregulin; Cofilin; Breast cancer cells; Dunn chamber assay; Transwell assay; F-actin binding and Depolymerization assays |
| Related URLs: | |
| Date Deposited: | 14 Dec 2009 13:50 |
| Last Modified: | 31 Jan 2013 01:02 |
| URI: | https://oak.novartis.com/id/eprint/967 |