Palmitoylation regulates raft affinity for the majority of integral raft proteins

被引:406
作者
Levental, Ilya [1 ]
Lingwood, Daniel [1 ]
Grzybek, Michal [1 ]
Coskun, Unal [1 ]
Simons, Kai [1 ]
机构
[1] Max Planck Inst Cell Biol & Genet, D-01307 Dresden, Germany
关键词
phase separation; raft partitioning; posttranslational modification; GPI-anchored protein; PLASMA-MEMBRANE VESICLES; GIANT UNILAMELLAR VESICLES; T-CELL-ACTIVATION; LIPID RAFTS; PHASE-SEPARATION; MODEL-MEMBRANE; DOMAINS; LOCALIZATION; HEMAGGLUTININ; ASSOCIATION;
D O I
10.1073/pnas.1016184107
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The physical basis for protein partitioning into lipid rafts remains an outstanding question in membrane biology that has previously been addressed only through indirect techniques involving differential solubilization by nonionic detergents. We have used giant plasma membrane vesicles, a plasma membrane model system that phase separates to include an ordered phase enriching for raft constituents, to measure the partitioning of the transmembrane linker for activation of T cells (LAT). LAT enrichment in the raft phase was dependent on palmitoylation at two juxtamembrane cysteines and could be enhanced by oligomerization. This palmitoylation requirement was also shown to regulate raft phase association for the majority of integral raft proteins. Because cysteine palmitoylation is the only lipid modification that has been shown to be reversibly regulated, our data suggest a role for palmitoylation as a dynamic raft targeting mechanism for transmembrane proteins.
引用
收藏
页码:22050 / 22054
页数:5
相关论文
共 38 条
[1]   SNAREs prefer liquid-disordered over "raft" (liquid-ordered) domains when reconstituted into giant unilamellar vesicles [J].
Bacia, K ;
Schuette, CG ;
Kahya, N ;
Jahn, R ;
Schwille, P .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (36) :37951-37955
[2]   Lipid rafts function in biosynthetic delivery of proteins to the cell surface in yeast [J].
Bagnat, M ;
Keränen, S ;
Shevchenko, A ;
Shevchenko, A ;
Simons, K .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (07) :3254-3259
[3]   Large-scale fluid/fluid phase separation of proteins and lipids in giant plasma membrane vesicles [J].
Baumgart, Tobias ;
Hammond, Adam T. ;
Sengupta, Prabuddha ;
Hess, Samuel T. ;
Holowka, David A. ;
Baird, Barbara A. ;
Webb, Watt W. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (09) :3165-3170
[4]   Partitioning of Thy-1, GM1, and cross-linked phospholipid analogs into lipid rafts reconstituted in supported model membrane monolayers [J].
Dietrich, C ;
Volovyk, ZN ;
Levi, M ;
Thompson, NL ;
Jacobson, K .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (19) :10642-10647
[5]   Quantitative analysis of phospholipids in functionally important membrane domains from RBL-2H3 mast cells using tandem high-resolution mass spectrometry [J].
Fridriksson, EK ;
Shipkova, PA ;
Sheets, ED ;
Holowka, D ;
Baird, B ;
McLafferty, FW .
BIOCHEMISTRY, 1999, 38 (25) :8056-8063
[6]   Crosslinking a lipid raft component triggers liquid ordered-liquid disordered phase separation in model plasma membranes [J].
Hammond, AT ;
Heberle, FA ;
Baumgart, T ;
Holowka, D ;
Baird, B ;
Feigenson, GW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (18) :6320-6325
[7]   Impaired activation and localization of LAT in anergic T cells as a consequence of a selective palmitoylation defect [J].
Hundt, Matthias ;
Tabata, Hiroki ;
Jeon, Myung-Shin ;
Hayashi, Keitaro ;
Tanaka, Yoshihiko ;
Krishna, Roma ;
De Giorgio, Lauren ;
Liu, Yun-Cai ;
Fukata, Masaki ;
Altman, Amnon .
IMMUNITY, 2006, 24 (05) :513-522
[8]   Palmitoylation-Dependent Plasma Membrane Transport but Lipid Raft-Independent Signaling by Linker for Activation of T Cells [J].
Hundt, Matthias ;
Harada, Yohsuke ;
De Giorgio, Lauren ;
Tanimura, Natsuko ;
Zhang, Weiguo ;
Altman, Amnon .
JOURNAL OF IMMUNOLOGY, 2009, 183 (03) :1685-1694
[9]   Temperature-dependent phase behavior and protein partioning in giant plasma membrane vesicles [J].
Johnson, S. A. ;
Stinson, B. M. ;
Go, M. S. ;
Carmona, L. M. ;
Reminick, J. I. ;
Fang, X. ;
Baumgart, T. .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2010, 1798 (07) :1427-1435
[10]   Raft partitioning and dynamic behavior of human placental alkaline phosphatase in giant unilamellar vesicles [J].
Kahya, N ;
Brown, DA ;
Schwille, P .
BIOCHEMISTRY, 2005, 44 (20) :7479-7489