Leep1 interacts with PIP3 and the Scar/WAVE complex to regulate cell migration and macropinocytosis.

摘要: Polarity is essential for diverse functions in many cell types. Establishing polarity requires targeting a network of specific signaling and cytoskeleton molecules to different subregions the cell, yet full complement regulators how their activities are integrated over space time form morphologically functionally distinct domains remain be uncovered. Here, by using model system Dictyostelium exploiting characteristic chemoattractant-stimulated translocation polarly distributed molecules, we developed proteomic screening approach, through which identified leucine-rich repeat domain-containing protein named Leep1 as novel regulator. We combined imaging, biochemical, phenotypic analyses demonstrate that localizes selectively at leading edge cells binding PIP3, where it modulates pseudopod macropinocytic cup dynamics negatively regulating Scar/WAVE complex. The spatiotemporal coordination PIP3 signaling, Leep1, complex provides cellular mechanism organizing protrusive structures edge.