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      Regulation of Transmembrane Signaling by Phase Separation

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      Annual Review of Biophysics

      Annual Reviews

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          Abstract

          Cell surface transmembrane receptors often form nanometer- to micrometer-scale clusters to initiate signal transduction in response to environmental cues. Extracellular ligand oligomerization, domain-domain interactions, and binding to multivalent proteins all contribute to cluster formation. Here we review the current understanding of mechanisms driving cluster formation in a series of representative receptor systems: glycosylated receptors, immune receptors, cell adhesion receptors, Wnt receptors, and receptor tyrosine kinases. We suggest that these clusters share properties of systems that undergo liquid–liquid phase separation and could be investigated in this light.

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          Lipid rafts as a membrane-organizing principle.

          Cell membranes display a tremendous complexity of lipids and proteins designed to perform the functions cells require. To coordinate these functions, the membrane is able to laterally segregate its constituents. This capability is based on dynamic liquid-liquid immiscibility and underlies the raft concept of membrane subcompartmentalization. Lipid rafts are fluctuating nanoscale assemblies of sphingolipid, cholesterol, and proteins that can be stabilized to coalesce, forming platforms that function in membrane signaling and trafficking. Here we review the evidence for how this principle combines the potential for sphingolipid-cholesterol self-assembly with protein specificity to selectively focus membrane bioactivity.
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            Fractal Concepts in Surface Growth

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              Polyvalent Interactions in Biological Systems: Implications for Design and Use of Multivalent Ligands and Inhibitors

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                Author and article information

                Affiliations
                [1 ]Department of Biophysics and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA;, ,
                Journal
                Annual Review of Biophysics
                Annu. Rev. Biophys.
                Annual Reviews
                1936-122X
                1936-1238
                May 06 2019
                May 06 2019
                : 48
                : 1
                : 465-494
                10.1146/annurev-biophys-052118-115534
                © 2019

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