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18.03.21 Filopodial dynamics emerges from diverse combinations of proteins

last modified Mar 21, 2021 10:25 PM
The Gallop lab tracked and measured filopodia and actin regulators in both in vivo and in vitro systems, and by incorporating theoretical modelling with Simons lab colleagues, identified a simple theory that explains how diverse combinations of tip complex proteins give rise to filopodia
18.03.21 Filopodial dynamics emerges from diverse combinations of proteins

Fig. 7A (excerpt): Time-lapse montage of filopodia growth in Drosophila embryo

Stochastic combinations of actin regulatory proteins are sufficient to drive filopodia formation

Dobramysl U et al. (2021) J Cell Biol 220: e202003052.

DOI: 10.1083/jcb.202003052.

 

Abstract from the paper

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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The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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