Tropomyosin Promotes Lamellipodial Persistence by Collaborating with Arp2/3 at the Leading Edge
| Autor: | Edna C. Hardeman, Galina Schevzov, James E. Bear, Nicole S. Bryce, Simon Brayford, Peter W. Gunning, Elizabeth M. Haynes |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Coronin Motility Tropomyosin macromolecular substances General Biochemistry Genetics and Molecular Biology Actin-Related Protein 2-3 Complex Article Polymerization 03 medical and health sciences Humans Protein Isoforms Pseudopodia Actin biology Cell migration Cofilin Fibroblasts Cell biology Actin Cytoskeleton 030104 developmental biology biology.protein Lamellipodium General Agricultural and Biological Sciences Cortactin |
| DOI: | 10.17615/t8xh-sd72 |
| Popis: | At the leading edge of migrating cells, protrusion of the lamellipodium is driven by Arp2/3-mediated polymerization of actin filaments [1]. This dense, branched actin network is promoted and stabilized by cortactin [2, 3]. In order to drive filament turnover, Arp2/3 networks are remodeled by proteins such as GMF, which blocks the actin-Arp2/3 interaction [4, 5], and coronin 1B, which acts by directing SSH1L to the lamellipodium where it activates the actin-severing protein cofilin [6, 7]. It has been shown in vitro that cofilin-mediated severing of Arp2/3 actin networks results in the generation of new pointed ends to which the actin-stabilizing protein tropomyosin (Tpm) can bind [8]. The presence of Tpm in lamellipodia, however, is disputed in the literature [9-19]. Here, we report that the Tpm isoforms 1.8/9 are enriched in the lamellipodium of fibroblasts as detected with a novel isoform-specific monoclonal antibody. RNAi-mediated silencing of Tpm1.8/9 led to an increase of Arp2/3 accumulation at the cell periphery and a decrease in the persistence of lamellipodia and cell motility, a phenotype consistent with cortactin- and coronin 1B-deficient cells [2, 7]. In the absence of coronin 1B or cofilin, Tpm1.8/9 protein levels are reduced while, conversely, inhibition of Arp2/3 with CK666 leads to an increase in Tpm1.8/9 protein. These findings establish a novel regulatory mechanism within the lamellipodium whereby Tpm collaborates with Arp2/3 to promote lamellipodial-based cell migration. |
| Databáze: | OpenAIRE |
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