
@article {62769,
	title = {A composition-dependent molecular clutch between T cell signaling condensates and actin.},
	journal = {Elife},
	volume = {8},
	year = {2019},
	month = {2019 Jul 03},
	abstract = {<p>During T cell activation, biomolecular condensates form at the immunological synapse (IS) through multivalency-driven phase separation of LAT, Grb2, Sos1, SLP-76, Nck, and WASP. These condensates move radially at the IS, traversing successive radially-oriented and concentric actin networks. To understand this movement, we biochemically reconstituted LAT condensates with actomyosin filaments. We found that basic regions of Nck and N-WASP/WASP promote association and co-movement of LAT condensates with actin, indicating conversion of weak individual affinities to high collective affinity upon phase separation. Condensates lacking these components were propelled differently, without strong actin adhesion. In cells, LAT condensates lost Nck as radial actin transitioned to the concentric network, and engineered condensates constitutively binding actin moved aberrantly. Our data show that Nck and WASP form a clutch between LAT condensates and actin in vitro and suggest that compositional changes may enable condensate movement by distinct actin networks in different regions of the IS.</p>
},
	issn = {2050-084X},
	doi = {10.7554/eLife.42695},
	author = {Ditlev, Jonathon A and Vega, Anthony R and K{\"o}ster, Darius Vasco and Su, Xiaolei and Tani, Tomomi and Lakoduk, Ashley M and Vale, Ronald D and Mayor, Satyajit and Jaqaman, Khuloud and Rosen, Michael K}
}
@article {66089,
	title = {Phosphorylation of Nephrin induces phase separated domains that move through actomyosin contraction.},
	journal = {Mol Biol Cell},
	year = {2019},
	month = {2019 Oct 10},
	pages = {mbcE18120823},
	abstract = {<p>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].</p>
},
	issn = {1939-4586},
	doi = {10.1091/mbc.E18-12-0823},
	author = {Kim, Soyeon and Kalappurakkal, Joseph M and Mayor, Satyajit and Rosen, Michael K}
}
