Effects of cholesterol depletion and increased lipid unsaturation on the properties of endocytic membranes

被引:87
作者
Hao, MM
Mukherjee, S
Sun, Y
Maxfield, FR
机构
[1] Cornell Univ, Weill Med Coll, Dept Biochem, New York, NY 10021 USA
[2] Columbia Univ, Dept Med, New York, NY 10032 USA
关键词
D O I
10.1074/jbc.M309793200
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
Lipid analogs with dialkylindocarbocyanine (DiI) head groups and short or unsaturated hydrocarbon chains (e.g. DiIC(12) and FAST DiI) enter the endocytic recycling compartment efficiently, whereas lipid analogs with long, saturated tails (e.g. DiIC(16) and DiIC(18)) are sorted out of this pathway and targeted to the late endosomes/lysosomes (Mukherjee, S., Soe, T. T., and Maxfield, F. R. ( 1999) J. Cell Biol. 144, 1271 - 1284). This differential trafficking of lipid analogs with the same polar head group was interpreted to result from differential partitioning to different types of domains with varying membrane order and/or curvature. Here we investigate the system further by monitoring the trafficking behavior of these lipid analogs under conditions that alter domain properties. There was a marked effect of cholesterol depletion on the cell-surface distribution and degree of internalization of the lipid probes. Furthermore, instead of going to the late endosomes/lysosomes as in control cells, long chain DiI analogs, such as DiIC16, were sorted to the recycling pathway in cholesterol-depleted cells. We confirmed that this difference was due to a change in overall membrane properties, and not cholesterol levels per se, by utilizing a Chinese hamster ovary cell line that overexpressed transfected stearoyl-CoA desaturase 1, a rate-limiting enzyme in the production of monounsaturated fatty acids. These cells have a decrease in membrane order because they contain a much larger fraction of unsaturated fatty acids. These cells showed alteration of DiI trafficking very similar to cholesterol-depleted cells. By using cold Triton X-100 extractability of different lipids as a criterion to determine the membrane properties of intracellular organelles, we found that the endocytic recycling compartment has abundant detergent-resistant membranes, in contrast to the late endosomes and lysosomes.
引用
收藏
页码:14171 / 14178
页数:8
相关论文
共 44 条
[11]   Cholesterol depletion induces large scale domain segregation in living cell membranes [J].
Hao, MM ;
Mukherjee, S ;
Maxfield, FR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (23) :13072-13077
[12]   Free fatty acids modulate intermembrane trafficking of cholesterol by increasing lipid mobilities:: Novel 13C NMR analyses of free cholesterol partitioning [J].
Johnson, RA ;
Hamilton, JA ;
Worgall, TS ;
Deckelbaum, RJ .
BIOCHEMISTRY, 2003, 42 (06) :1637-1645
[13]   Shape transformations of vesicles with intramembrane domains [J].
Julicher, F ;
Lipowsky, R .
PHYSICAL REVIEW E, 1996, 53 (03) :2670-2683
[14]   SORTING OF SPHINGOLIPIDS IN THE ENDOCYTIC PATHWAY OF HT29 CELLS [J].
KOK, JW ;
BABIA, T ;
HOEKSTRA, D .
JOURNAL OF CELL BIOLOGY, 1991, 114 (02) :231-239
[15]  
KOK JW, 1990, EUR J CELL BIOL, V53, P173
[16]   LIPID RECYCLING BETWEEN THE PLASMA-MEMBRANE AND INTRACELLULAR COMPARTMENTS - TRANSPORT AND METABOLISM OF FLUORESCENT SPHINGOMYELIN ANALOGS IN CULTURED FIBROBLASTS [J].
KOVAL, M ;
PAGANO, RE .
JOURNAL OF CELL BIOLOGY, 1989, 108 (06) :2169-2181
[17]   Insolubility of lipids in Triton X-100: physical origin and relationship to sphingolipid/cholesterol membrane domains (rafts) [J].
London, E ;
Brown, DA .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2000, 1508 (1-2) :182-195
[18]   Membrane domains and polarized trafficking of sphingolipids [J].
Maier, O ;
Slimane, TA ;
Hoekstra, D .
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2001, 12 (02) :149-161
[19]   Endocytosis and sorting of glycosphingolipids in sphingolipid storage disease [J].
Marks, DL ;
Pagano, RE .
TRENDS IN CELL BIOLOGY, 2002, 12 (12) :605-613
[20]   SORTING OF MEMBRANE-COMPONENTS FROM ENDOSOMES AND SUBSEQUENT RECYCLING TO THE CELL-SURFACE OCCURS BY A BULK FLOW PROCESS [J].
MAYOR, S ;
PRESLEY, JF ;
MAXFIELD, FR .
JOURNAL OF CELL BIOLOGY, 1993, 121 (06) :1257-1269