Phosphorylation of nephrin induces phase separated domains that move through actomyosin contraction
Kalappurakkal, Joseph Mathew
Rosen, Michael K.
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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.
© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Kim, S., Kalappurakkal, J. M., Mayor, S., & Rosen, M. K. Phosphorylation of nephrin induces phase separated domains that move through actomyosin contraction. Molecular Biology of the Cell, 30(24), (2019): 2996–3012, doi:10.1091/mbc.E18-12-0823.
Suggested CitationKim, S., Kalappurakkal, J. M., Mayor, S., & Rosen, M. K. (2019). Phosphorylation of nephrin induces phase separated domains that move through actomyosin contraction. Molecular Biology of the Cell, 30(24), 2996–3012.
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