Stochastic combinations of actin regulatory proteins are sufficient to drive filopodia formation |
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| Authors: | Ulrich Dobramysl Iris Katharina Jarsch Yoshiko Inoue Hanae Shimo Benjamin Richier Jonathan R Gadsby Julia Mason Alicja Sza&#x;apak Pantelis Savvas Ioannou Guilherme Pereira Correia Astrid Walrant Richard Butler Edouard Hannezo Benjamin D Simons Jennifer L Gallop |
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| Institution: | 1.Gurdon Institute, University of Cambridge, Cambridge, UK;2.Department of Biochemistry, University of Cambridge, Cambridge, UK;3.Institute of Science and Technology Austria, Klosterneuburg, Austria;4.Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge, UK |
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| Abstract: | Assemblies of actin and its regulators underlie the dynamic morphology of all eukaryotic cells. To understand how actin regulatory proteins work together to generate actin-rich structures such as filopodia, we analyzed the localization of diverse actin regulators within filopodia in Drosophila embryos and in a complementary in vitro system of filopodia-like structures (FLSs). We found that the composition of the regulatory protein complex where actin is incorporated (the filopodial tip complex) is remarkably heterogeneous both in vivo and in vitro. Our data reveal that different pairs of proteins correlate with each other and with actin bundle length, suggesting the presence of functional subcomplexes. This is consistent with a theoretical framework where three or more redundant subcomplexes join the tip complex stochastically, with any two being sufficient to drive filopodia formation. We provide an explanation for the observed heterogeneity and suggest that a mechanism based on multiple components allows stereotypical filopodial dynamics to arise from diverse upstream signaling pathways. |
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