TY - JOUR
T1 - BAR scaffolds drive membrane fission by crowding disordered domains
AU - Snead, Wilton T.
AU - Zeno, Wade F.
AU - Kago, Grace
AU - Perkins, Ryan W.
AU - Blair Richter, J.
AU - Zhao, Chi
AU - Lafer, Eileen M.
AU - Stachowiak, Jeanne C.
N1 - Funding Information:
J.C. Stachowiak and E.M. Lafer acknowledge funding from the National Institutes of Health (R01GM112065), including an administrative supplement for diversity in support of W.F. Zeno. W.T. Snead acknowledges the support of a Ruth L. Kirschstein National Research Service Award Predoctoral Fellowship from the National Institutes of Health (F31GM121013), as well as a fellowship from the Graduate School, University of Texas at Austin. G. Kago acknowledges the support of a National Science Foundation Graduate Research Fellowship (DGE-1610403). We acknowledge the support of the University of Texas Health Science Center at San Antonio Center for Macromolecular Interactions, which is supported by the Mays Cancer Center through the National Cancer Institute (P30 grant CA054174), and Texas state funds provided through the Office of the Vice President for Research of the University of Texas Health Science Center at San Antonio. The authors declare no competing financial interests.
Publisher Copyright:
© 2018 Sawyer et al.
PY - 2019/2/1
Y1 - 2019/2/1
N2 - Cellular membranes are continuously remodeled. Te crescent-shaped bin-amphiphysin-rvs (BAR) domains remodel membranes in multiple cellular pathways. Based on studies of isolated BAR domains in vitro, the current paradigm is that BAR domain-containing proteins polymerize into cylindrical scaffolds that stabilize lipid tubules. But in nature, proteins that contain BAR domains ofen also contain large intrinsically disordered regions. Using in vitro and live cell assays, here we show that full-length BAR domain-containing proteins, rather than stabilizing membrane tubules, are instead surprisingly potent drivers of membrane fssion. Specifcally, when BAR scaffolds assemble at membrane surfaces, their bulky disordered domains become crowded, generating steric pressure that destabilizes lipid tubules. More broadly, we observe this behavior with BAR domains that have a range of curvatures. Tese data suggest that the ability to concentrate disordered domains is a key driver of membrane remodeling and fssion by BAR domain-containing proteins.
AB - Cellular membranes are continuously remodeled. Te crescent-shaped bin-amphiphysin-rvs (BAR) domains remodel membranes in multiple cellular pathways. Based on studies of isolated BAR domains in vitro, the current paradigm is that BAR domain-containing proteins polymerize into cylindrical scaffolds that stabilize lipid tubules. But in nature, proteins that contain BAR domains ofen also contain large intrinsically disordered regions. Using in vitro and live cell assays, here we show that full-length BAR domain-containing proteins, rather than stabilizing membrane tubules, are instead surprisingly potent drivers of membrane fssion. Specifcally, when BAR scaffolds assemble at membrane surfaces, their bulky disordered domains become crowded, generating steric pressure that destabilizes lipid tubules. More broadly, we observe this behavior with BAR domains that have a range of curvatures. Tese data suggest that the ability to concentrate disordered domains is a key driver of membrane remodeling and fssion by BAR domain-containing proteins.
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U2 - 10.1083/jcb.201807119
DO - 10.1083/jcb.201807119
M3 - Article
C2 - 30504247
AN - SCOPUS:85061046036
SN - 0021-9525
VL - 218
SP - 664
EP - 682
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 2
ER -