RRC ID 70470
Author Honda G, Saito N, Fujimori T, Hashimura H, Nakamura MJ, Nakajima A, Sawai S.
Title Microtopographical guidance of macropinocytic signaling patches.
Journal Proc Natl Acad Sci U S A
Abstract 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.
Volume 118(50)
Published 2021-12-14
DOI 10.1073/pnas.2110281118
PII 2110281118
PMID 34876521
PMC PMC8685668
MeSH Cell Membrane / physiology Chemotaxis Computer Simulation* Dictyostelium / physiology* Models, Biological* Movement Phosphatidylinositol 3-Kinases Pinocytosis / physiology* Signal Transduction
IF 9.412
Resource
Cellular slime molds G90576 G90623 S00405 DBS0236830 S00100 S00404 S90641