Membrane-sculpting BAR domains generate stable lipid microdomains.
Bin-Amphiphysin-Rvs (BAR) domain proteins are central regulators of many cellular processes involving membrane dynamics. BAR domains sculpt phosphoinositide-rich membranes to generate membrane protrusions or invaginations. Here, we report that, in addition to regulating membrane geometry, BAR domains can generate extremely stable lipid microdomains by "freezing" phosphoinositide dynamics. This is a general feature of BAR domains, because the yeast endocytic BAR and Fes/CIP4 homology BAR (F-BAR) domains, the inverse BAR domain of Pinkbar, and the eisosomal BAR protein Lsp1 induced phosphoinositide clustering and halted lipid diffusion, despite differences in mechanisms of membrane interactions. Lsp1 displays comparable low diffusion rates in vitro and in vivo, suggesting that BAR domain proteins also generate stable phosphoinositide microdomains in cells. These results uncover a conserved role for BAR superfamily proteins in regulating lipid dynamics within membranes. Stable microdomains induced by BAR domain scaffolds and specific lipids can generate phase boundaries and diffusion barriers, which may have profound impacts on diverse cellular processes.
Institute of Biotechnology, University of Helsinki, 00014 Helsinki, Finland.
Hongxia
H
Zhao
Alphée
A
Michelot
Essi V
EV
Koskela
Vadym
V
Tkach
Dimitrios
D
Stamou
David G
DG
Drubin
Pekka
P
Lappalainen
D002462:Cell Membrane / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000378:metabolism*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
D008563:Membrane Lipids; D008565:Membrane Proteins; D046912:Multiprotein Complexes