TY - JOUR
T1 - Coupling of protein condensates to ordered lipid domains determines functional membrane organization
AU - Wang, Hong Yin
AU - Chan, Sze Ham
AU - Dey, Simli
AU - Castello-Serrano, Ivan
AU - Rosen, Michael K.
AU - Ditlev, Jonathon A.
AU - Levental, Kandice R.
AU - Levental, Ilya
N1 - Publisher Copyright:
Copyright © 2023 The Authors, some rights reserved.
PY - 2023/4
Y1 - 2023/4
N2 - During T cell activation, the transmembrane adaptor protein LAT (linker for activation of T cells) forms biomolecular condensates with Grb2 and Sos1, facilitating signaling. LAT has also been associated with cholesterol-rich condensed lipid domains; However, the potential coupling between protein condensation and lipid phase separation and its role in organizing T cell signaling were unknown. Here, we report that LAT/Grb2/Sos1 condensates reconstituted on model membranes can induce and template lipid domains, indicating strong coupling between lipid- and protein-based phase separation. Correspondingly, activation of T cells induces cytoplasmic protein condensates that associate with and stabilize raft-like membrane domains. Inversely, lipid domains nucleate and stabilize LAT protein condensates in both reconstituted and living systems. This coupling of lipid and protein assembly is functionally important, as uncoupling of lipid domains from cytoplasmic protein condensates abrogates T cell activation. Thus, thermodynamic coupling between protein condensates and ordered lipid domains regulates the functional organization of living membranes.
AB - During T cell activation, the transmembrane adaptor protein LAT (linker for activation of T cells) forms biomolecular condensates with Grb2 and Sos1, facilitating signaling. LAT has also been associated with cholesterol-rich condensed lipid domains; However, the potential coupling between protein condensation and lipid phase separation and its role in organizing T cell signaling were unknown. Here, we report that LAT/Grb2/Sos1 condensates reconstituted on model membranes can induce and template lipid domains, indicating strong coupling between lipid- and protein-based phase separation. Correspondingly, activation of T cells induces cytoplasmic protein condensates that associate with and stabilize raft-like membrane domains. Inversely, lipid domains nucleate and stabilize LAT protein condensates in both reconstituted and living systems. This coupling of lipid and protein assembly is functionally important, as uncoupling of lipid domains from cytoplasmic protein condensates abrogates T cell activation. Thus, thermodynamic coupling between protein condensates and ordered lipid domains regulates the functional organization of living membranes.
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U2 - 10.1126/sciadv.adf6205
DO - 10.1126/sciadv.adf6205
M3 - Article
C2 - 37126554
AN - SCOPUS:85158071502
SN - 2375-2548
VL - 9
JO - Science Advances
JF - Science Advances
IS - 17
M1 - eadf6205
ER -