Protein sorting by lipid phase-like domains supports emergent signaling function in B lymphocyte plasma membranes.
Diverse cellular signaling events, including B cell receptor (BCR) activation, are hypothesized to be facilitated by domains enriched in specific plasma membrane lipids and proteins that resemble liquid-ordered phase-separated domains in model membranes. This concept remains controversial and lacks direct experimental support in intact cells. Here, we visualize ordered and disordered domains in mouse B lymphoma cell membranes using super-resolution fluorescence localization microscopy, demonstrate that clustered BCR resides within ordered phase-like domains capable of sorting key regulators of BCR activation, and present a minimal, predictive model where clustering receptors leads to their collective activation by stabilizing an extended ordered domain. These results provide evidence for the role of membrane domains in BCR signaling and a plausible mechanism of BCR activation via receptor clustering that could be generalized to other signaling pathways. Overall, these studies demonstrate that lipid mediated forces can bias biochemical networks in ways that broadly impact signal transduction.
Department of Biophysics, University of Michigan, Ann Arbor, United States.
Matthew B
0000-0001-8858-4239
MB
Stone
Department of Biophysics, University of Michigan, Ann Arbor, United States.
Sarah A
SA
Shelby
Department of Biophysics, University of Michigan, Ann Arbor, United States.
Marcos F
MF
Núñez
Department of Biophysics, University of Michigan, Ann Arbor, United States.
Kathleen
K
Wisser
Department of Biophysics, University of Michigan, Ann Arbor, United States.
Sarah L
0000-0002-9317-2308
SL
Veatch
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D021381:Protein Transport; D015398:Signal Transduction
D008563:Membrane Lipids
biophysics; immunology; lipid raft; membrane phase seperation; mouse; structural biology; super-resolution microscopy