Dobramysl, Ulrich; Jarsch, Iris Katharina; Inoue, Yoshiko; Shimo, Hanae; Richier, Benjamin; Gadsby, Jonathan R.; Mason, Julia; Szałapak, Alicja; Ioannou, Pantelis Savvas; Correia, Guilherme Pereira; Walrant, Astrid; Butler, Richard
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.
Journal of Cell Biology
This work was supported by European Research Council grant 281971, Wellcome Trust Research Career Development Fellowship WT095829AIA and Wellcome Trust Senior Research Fellowship 219482/Z/19/Z to J.L. Gallop, a Wellcome Trust Senior Investigator Award 098357 to B.D. Simons, and an Austrian Science Fund grant (P31639) to E. Hannezo. We acknowledge core funding by the Wellcome Trust (092096) and Cancer Research UK (C6946/A14492). U. Dobramysl was supported by a Wellcome Trust Junior Interdisciplinary Fellowship grant (105602/Z/14/Z) and a Herchel Smith Postdoctoral Fellowship. H. Shimo was supported by a Funai Foundation Overseas scholarship.
Dobramysl U, Jarsch IK, Inoue Y, et al. Stochastic combinations of actin regulatory proteins are sufficient to drive filopodia formation. Journal of Cell Biology. 2021;220(4). doi:10.1083/jcb.202003052
Dobramysl, U., Jarsch, I. K., Inoue, Y., Shimo, H., Richier, B., Gadsby, J. R., … Gallop, J. L. (2021). Stochastic combinations of actin regulatory proteins are sufficient to drive filopodia formation. Journal of Cell Biology. Rockefeller University Press. https://doi.org/10.1083/jcb.202003052
Dobramysl, Ulrich, Iris Katharina Jarsch, Yoshiko Inoue, Hanae Shimo, Benjamin Richier, Jonathan R. Gadsby, Julia Mason, et al. “Stochastic Combinations of Actin Regulatory Proteins Are Sufficient to Drive Filopodia Formation.” Journal of Cell Biology. Rockefeller University Press, 2021. https://doi.org/10.1083/jcb.202003052.
U. Dobramysl et al., “Stochastic combinations of actin regulatory proteins are sufficient to drive filopodia formation,” Journal of Cell Biology, vol. 220, no. 4. Rockefeller University Press, 2021.
Dobramysl U, Jarsch IK, Inoue Y, Shimo H, Richier B, Gadsby JR, Mason J, Szałapak A, Ioannou PS, Correia GP, Walrant A, Butler R, Hannezo EB, Simons BD, Gallop JL. 2021. Stochastic combinations of actin regulatory proteins are sufficient to drive filopodia formation. Journal of Cell Biology. 220(4), e202003052.
Dobramysl, Ulrich, et al. “Stochastic Combinations of Actin Regulatory Proteins Are Sufficient to Drive Filopodia Formation.” Journal of Cell Biology, vol. 220, no. 4, e202003052, Rockefeller University Press, 2021, doi:10.1083/jcb.202003052.
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