title: Multi-protein assemblies underlie the mesoscale organization of the plasma membrane.
abstract: Most proteins have uneven distributions in the plasma membrane. Broadly speaking, this may be caused by mechanisms specific to each protein, or may be a consequence of a general pattern that affects the distribution of all membrane proteins. The latter hypothesis has been difficult to test in the past. Here, we introduce several approaches based on click chemistry, through which we study the distribution of membrane proteins in living cells, as well as in membrane sheets. We found that the plasma membrane proteins form multi-protein assemblies that are long lived (minutes), and in which protein diffusion is restricted. The formation of the assemblies is dependent on cholesterol. They are separated and anchored by the actin cytoskeleton. Specific proteins are preferentially located in different regions of the assemblies, from their cores to their edges. We conclude that the assemblies constitute a basic mesoscale feature of the membrane, which affects the patterning of most membrane proteins, and possibly also their activity.
authors: 1] Department of Neuro- and Sensory Physiology, University of Göttingen Medical Centre, and Centre for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), 37075 Göttingen, Germany [2] International Max Planck Research School Molecular Biology, 37077 Göttingen, Germany.
authors: Sinem K
authors: SK
authors: Saka
authors: Department of Nanobiophotonics, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
authors: Alf
authors: A
authors: Honigmann
authors: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford OX3 9DS, UK.
authors: Christian
authors: C
authors: Eggeling
authors: Department of Nanobiophotonics, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
authors: Stefan W
authors: SW
authors: Hell
authors: Department of Membrane Biochemistry, Life and Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany.
authors: Thorsten
authors: T
authors: Lang
authors: Department of Neuro- and Sensory Physiology, University of Göttingen Medical Centre, and Centre for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), 37075 Göttingen, Germany.
authors: Silvio O
authors: SO
authors: Rizzoli
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002459:Cell Fusion; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D002522:Chlorocebus aethiops; D002784:Cholesterol / Q000378:metabolism; D057930:Click Chemistry; D003599:Cytoskeleton / Q000378:metabolism; D036681:Fluorescence Recovery After Photobleaching / Q000379:methods; D008565:Membrane Proteins / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats
chemical_list: D000199:Actins; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D002784:Cholesterol