Phosphorylation of nephrin induces phase separated domains that move through actomyosin contraction.

Soyeon Kim, Joseph M Kalappurakkal, Satyajit Mayor, Michael K Rosen

Molecular biology of the cell 2019 Nov 15

filter terms:

The plasma membrane of eukaryotic cells is organized into lipid and protein microdomains, whose assembly mechanisms and functions are incompletely understood. We demonstrate that proteins in the nephrin/Nck/N-WASP actin-regulatory pathway cluster into micron-scale domains at the basal plasma membrane upon triggered phosphorylation of transmembrane protein nephrin. The domains are persistent but readily exchange components with their surroundings, and their formation is dependent on the number of Nck SH3 domains, suggesting they are phase separated polymers assembled through multivalent interactions among the three proteins. The domains form independent of the actin cytoskeleton, but acto-myosin contractility induces their rapid lateral movement. Nephrin phosphorylation induces larger clusters at the cell periphery, which are associated with extensive actin assembly and dense filopodia. Our studies illustrate how multivalent interactions between proteins at the plasma membrane can produce micron-scale organization of signaling molecules, and how the resulting clusters can both respond to and control the actin cytoskeleton.

Citation

Soyeon Kim, Joseph M Kalappurakkal, Satyajit Mayor, Michael K Rosen. Phosphorylation of nephrin induces phase separated domains that move through actomyosin contraction. Molecular biology of the cell. 2019 Nov 15;30(24):2996-3012