The Range of Cooperativity Modulates Actin Binding Protein Cluster Size, Density and Dynamics
| Autor: | Goff, Thomas Le, Michelot, Alphée |
|---|---|
| Rok vydání: | 2018 |
| Předmět: | |
| Druh dokumentu: | Working Paper |
| Popis: | The actin cytoskeleton is composed of multiple networks which are specialized for several processes such as cell motility or cell division. Each of these networks are composed of organized actin microfilaments which are decorated with specific sets of actin binding proteins (ABPs). The molecular mechanisms guiding ABPs to specific actin networks are still poorly understood, but cooperativity, the mechanism by which the binding of an ABP is positively influenced by proximal bound ABPs, plays a crucial role in generating locally dense stretches of ABPs. Cooperative binding is characterized by its amplitude, but also by the range at which its effects are propagated along an actin filament through long-range allosteric interactions. The range of these allosteric effects is still debated, but is likely to be significant at the lengthscale of actin filaments in cells. Here, we investigated how cooperativity influences the clustering of ABPs, using a stochastic computational model of binding of ABPs to actin filaments. The model reproduces the formation of ABP clusters observed experimentally at the single filament scale, and provides a theoretical estimation of the range of cooperativity for proteins such as ADF/cofilin. We found that both the amplitude and the spatial range of cooperativity dramatically impact the properties of clustering. However, the parameters of cooperativity modulate differently the rate of assembly, size and dynamics of the ABP clusters, suggesting that cooperativity is an efficient mechanism to regulate precisely the recruitment of ABPs in cells. This work provides a more general framework for future understanding of how actin networks acquire distinct and specific protein compositions from a common cytoplasm. Comment: 7 figures in main text + 3 figures in supplementary material |
| Databáze: | arXiv |
| Externí odkaz: |
|