Microtopographical guidance of macropinocytic signaling patches
| Autor: | Gen Honda, Nen Saito, Taihei Fujimori, Hidenori Hashimura, Mitsuru J. Nakamura, Akihiko Nakajima, Satoshi Sawai |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.2110281118 |
| Popis: | Significance Morphologies of amoebae and immune cells are highly deformable and dynamic, which facilitates migration in various terrains, as well as ingestion of extracellular solutes and particles. It remains largely unexplored whether and how the underlying membrane protrusions are triggered and guided by the geometry of the surface in contact. In this study, we show that in Dictyostelium, the precursor of a structure called macropinocytic cup, which has been thought to be a constitutive process for the uptake of extracellular fluid, is triggered by micrometer-scale surface features. Imaging analysis and computational simulations demonstrate how the topographical dependence of the self-organizing dynamics supports efficient guidance and capturing of the membrane protrusion and hence movement of an entire cell along such surface features. In fast-moving cells such as amoeba and immune cells, dendritic actin filaments are spatiotemporally regulated to shape large-scale plasma membrane protrusions. Despite their importance in migration, as well as in particle and liquid ingestion, how their dynamics are affected by micrometer-scale features of the contact surface is still poorly understood. Here, through quantitative image analysis of Dictyostelium on microfabricated surfaces, we show that there is a distinct mode of topographical guidance directed by the macropinocytic membrane cup. Unlike other topographical guidance known to date that depends on nanometer-scale curvature sensing protein or stress fibers, the macropinocytic membrane cup is driven by the Ras/PI3K/F-actin signaling patch and its dependency on the micrometer-scale topographical features, namely PI3K/F-actin–independent accumulation of Ras-GTP at the convex curved surface, PI3K-dependent patch propagation along the convex edge, and its actomyosin-dependent constriction at the concave edge. Mathematical model simulations demonstrate that the topographically dependent initiation, in combination with the mutually defining patch patterning and the membrane deformation, gives rise to the topographical guidance. Our results suggest that the macropinocytic cup is a self-enclosing structure that can support liquid ingestion by default; however, in the presence of structured surfaces, it is directed to faithfully trace bent and bifurcating ridges for particle ingestion and cell guidance. |
| Databáze: | OpenAIRE |
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