TitlePhosphorylation of Nephrin induces phase separated domains that move through actomyosin contraction.
Publication TypeJournal Article
Year of Publication2019
AuthorsKim S, Kalappurakkal JM, Mayor S, Rosen MK
JournalMol Biol Cell
PaginationmbcE18120823
Date Published2019 Oct 10
ISSN1939-4586
Abstract

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 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. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text].

DOI10.1091/mbc.E18-12-0823
Alternate JournalMol. Biol. Cell
PubMed ID31599693