Transbilayer Lipid Interactions Mediate Nanoclustering of Lipid-Anchored Proteins

被引：295

作者：

Raghupathy, Riya ^{[1
,3
]}

Anilkumar, Anupama Ambika ^{[1
,3
]}

Polley, Anirban ^{[2
,8
]}

Singh, Parvinder Pal ^{[6
]}

Yadav, Mahipal ^{[6
]}

Johnson, Charles ^{[5
]}

Suryawanshi, Sharad ^{[5
]}

Saikam, Varma ^{[6
]}

Sawant, Sanghapal D. ^{[6
]}

Panda, Aniruddha ^{[1
,7
]}

Guo, Zhongwu ^{[5
]}

Vishwakarma, Ram A. ^{[6
]}

Rao, Madan ^{[1
,2
]}

Mayor, Satyajit ^{[1
,4
]}

机构：

[1] Natl Ctr Biol Sci TIFR, Bangalore 560065, Karnataka, India

[2] Raman Res Inst, Bangalore 560080, Karnataka, India

[3] Shanmugha Arts Sci Technol & Res Acad, Thanjavur 613401, India

[4] Inst Stem Cell Biol & Regenerat Med, Bangalore 560065, Karnataka, India

[5] Wayne State Univ, Detroit, MI 48202 USA

[6] Indian Inst Integrat Med CSIR, Jammu 180001, India

[7] Manipal Univ, Manipal 576104, Karnataka, India

[8] Tampere Univ Technol, Tampere 33720, Finland

来源：

CELL | 2015年 / 161卷 / 03期

基金：

美国国家科学基金会;

关键词：

CELL-SURFACE MOLECULES; PLASMA-MEMBRANE; NANOSCALE ORGANIZATION; INDEPENDENT ENDOCYTOSIS; PHOSPHOLIPASE-C; PHOSPHATIDYLSERINE; RECEPTOR; DOMAINS; BIOSYNTHESIS; VESICLES;

D O I：

10.1016/j.cell.2015.03.048

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Understanding how functional lipid domains in live cell membranes are generated has posed a challenge. Here, we show that transbilayer interactions are necessary for the generation of cholesterol-dependent nanoclusters of GPI-anchored proteins mediated by membrane-adjacent dynamic actin filaments. We find that long saturated acyl-chains are required for forming GPI-anchor nanoclusters. Simultaneously, at the inner leaflet, long acyl-chain-containing phosphatidylserine (PS) is necessary for transbilayer coupling. All-atom molecular dynamics simulations of asymmetric multicomponent-membrane bilayers in a mixed phase provide evidence that immobilization of long saturated acyl-chain lipids at either leaflet stabilizes cholesterol-dependent transbilayer interactions forming local domains with characteristics similar to a liquid-ordered (lo) phase. This is verified by experiments wherein immobilization of long acyl-chain lipids at one leaflet effects transbilayer interactions of corresponding lipids at the opposite leaflet. This suggests a general mechanism for the generation and stabilization of nanoscale cholesterol-dependent and actin-mediated lipid clusters in live cell membranes.

引用

页码：581 / 594

页数：14

共 52 条

[1] Phosphatidylserine binding sites in red cell spectrin [J].

An, XL ;

Guo, XH ;

Wu, Y ;

Mohandas, N .

BLOOD CELLS MOLECULES AND DISEASES, 2004, 32 (03) :430-432

[2] Fluorescently labeled neomycin as a probe of phosphatidylinositol-4,5-bisphosphate in membranes [J].

Arbuzova, A ;

Martushova, K ;

Hangyás-Mihályné, G ;

Morris, AJ ;

Ozaki, S ;

Prestwich, GD ;

McLaughlin, S .

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2000, 1464 (01) :35-48

[3] Caveolae regulate the nanoscale organization of the plasma membrane to remotely control Ras signaling [J].

Ariotti, Nicholas ;

Fernandez-Rojo, Manuel A. ;

Zhou, Yong ;

Hill, Michelle M. ;

Rodkey, Travis L. ;

Inder, Kerry L. ;

Tanner, Lukas B. ;

Wenk, Markus R. ;

Hancock, John F. ;

Parton, Robert G. .

JOURNAL OF CELL BIOLOGY, 2014, 204 (05) :777-792

[4] 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

[5]

BLIGH EG, 1959, CAN J BIOCHEM PHYS, V37, P911

[6] Improved detection and characterization of paroxysmal nocturnal hemoglobinuria using fluorescent aerolysin [J].

Brodsky, RA ;

Mukhina, GL ;

Li, SY ;

Nelson, KL ;

Chiurazzi, PL ;

Buckley, JT ;

Borowitz, MJ .

AMERICAN JOURNAL OF CLINICAL PATHOLOGY, 2000, 114 (03) :459-466

[7] Phospholipase A2 structure/function, mechanism, and signaling [J].

Burke, John E. ;

Dennis, Edward A. .

JOURNAL OF LIPID RESEARCH, 2009, 50 :S237-S242

[8] Spatiotemporal regulation of chemical reactions by active cytoskeletal remodeling [J].

Chaudhuri, Abhishek ;

Bhattacharya, Bhaswati ;

Gowrishankar, Kripa ;

Mayor, Satyajit ;

Rao, Madan .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (36) :14825-14830

[9] Regulation of human EGF receptor by lipids [J].

Coskun, Unal ;

Grzybek, Michal ;

Drechsel, David ;

Simons, Kai .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (22) :9044-9048

[10] Gangliosides GM1 and GM3 in the living cell membrane form clusters susceptible to cholesterol depletion and chilling [J].

Fujita, Akikazu ;

Cheng, Jinglei ;

Hirakawa, Minako ;

Furukawa, Koichi ;

Kusunoki, Susumu ;

Fujimoto, Toyoshi .

MOLECULAR BIOLOGY OF THE CELL, 2007, 18 (06) :2112-2122

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