: Plasma membrane heterogeneity has been tied to a litany of cellular functions and is often explained by analogy to membrane phase separation; however, models based on phase separation alone fall short of describing the rich organization available within cell membranes. Here we present comprehensive experimental evidence motivating an updated model of plasma membrane heterogeneity in which membrane domains assemble in response to protein scaffolds. Quantitative super-resolution nanoscopy measurements in live B lymphocytes detect membrane domains that emerge upon clustering B cell receptors (BCRs). These domains enrich and retain membrane proteins based on their preference for the liquid-ordered phase. Unlike phase-separated membranes that consist of binary phases with defined compositions, membrane composition at BCR clusters is modulated through the protein constituents in clusters and the composition of the membrane overall. This tunable domain structure is detected through the variable sorting of membrane probes and impacts the magnitude of BCR activation.

Membrane phase separation drives responsive assembly of receptor signaling domains / Shelby, S. A.; Castello-Serrano, Ivan.; Wisser, K. C.; Levental, I.; Veatch, S. L.. - In: NATURE CHEMICAL BIOLOGY. - ISSN 1552-4469. - 19:6(2023), pp. 750-758. [10.1038/s41589-023-01268-8]

Membrane phase separation drives responsive assembly of receptor signaling domains

Castello-Serrano Ivan.;
2023-01-01

Abstract

: Plasma membrane heterogeneity has been tied to a litany of cellular functions and is often explained by analogy to membrane phase separation; however, models based on phase separation alone fall short of describing the rich organization available within cell membranes. Here we present comprehensive experimental evidence motivating an updated model of plasma membrane heterogeneity in which membrane domains assemble in response to protein scaffolds. Quantitative super-resolution nanoscopy measurements in live B lymphocytes detect membrane domains that emerge upon clustering B cell receptors (BCRs). These domains enrich and retain membrane proteins based on their preference for the liquid-ordered phase. Unlike phase-separated membranes that consist of binary phases with defined compositions, membrane composition at BCR clusters is modulated through the protein constituents in clusters and the composition of the membrane overall. This tunable domain structure is detected through the variable sorting of membrane probes and impacts the magnitude of BCR activation.
2023
Membrane phase separation drives responsive assembly of receptor signaling domains / Shelby, S. A.; Castello-Serrano, Ivan.; Wisser, K. C.; Levental, I.; Veatch, S. L.. - In: NATURE CHEMICAL BIOLOGY. - ISSN 1552-4469. - 19:6(2023), pp. 750-758. [10.1038/s41589-023-01268-8]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2978372
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 46
  • ???jsp.display-item.citation.isi??? 43
social impact