Endogenous adipocyte apolipoprotein E is colocalized with caveolin at the adipocyte plasma membrane
Apolipoprotein (apo)E is well established as a secreted protein that plays an important role in systemic lipoprotein metabolism and vascular wall homeostasis. Recently, endogenous expression of apoE in adipocytes has been shown to play an important role in adipocyte lipoprotein metabolism and gene e...
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doaj-f30e62b3fc3449299c29d0645c84ca792021-04-28T06:03:44ZengElsevierJournal of Lipid Research0022-22752011-03-01523489498Endogenous adipocyte apolipoprotein E is colocalized with caveolin at the adipocyte plasma membraneLili Yue0Theodore Mazzone1Departments of Medicine, Pharmacology, University of Illinois at Chicago, Chicago, IL 60612To whom correspondence should be addressed. tmazzone@uic.edu; Departments of Medicine, Pharmacology, University of Illinois at Chicago, Chicago, IL 60612; Departments of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL 60612Apolipoprotein (apo)E is well established as a secreted protein that plays an important role in systemic lipoprotein metabolism and vascular wall homeostasis. Recently, endogenous expression of apoE in adipocytes has been shown to play an important role in adipocyte lipoprotein metabolism and gene expression consistent with a nonsecreted cellular itinerary for apoE. We designed studies to evaluate if adipocyte apoE was retained as a constituent protein in adipocytes and to identify a cellular retention compartment. Using confocal microscopy, coimmunoprecipitation, and sucrose density cellular fractionation, we establish that endogenous apoE shares a cellular itinerary with the constituent protein caveolin-1. Altering adipocyte caveolar number by modulating cellular cholesterol flux or altering caveolin expression regulates the distribution of cellular apoE between cytoplasmic and plasma membrane compartments. A mechanism for colocalization of apoE with caveolin was established by demonstrating a noncovalent interaction between an aromatic amino acid-enriched apoE N-terminal domain with the caveolin scaffolding domain. Absent apoE expression in adipocytes alters caveolar lipid composition. These observations provide evidence for an interaction between two proteins involved in cellular lipid metabolism in a cell specialized for lipid storage and flux, and rationalize a biological basis for the impact of adipocyte apoE expression on adipocyte lipoprotein metabolism.http://www.sciencedirect.com/science/article/pii/S0022227520409290adipocytesadipose tissuecaveolaeobesity |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lili Yue Theodore Mazzone |
spellingShingle |
Lili Yue Theodore Mazzone Endogenous adipocyte apolipoprotein E is colocalized with caveolin at the adipocyte plasma membrane Journal of Lipid Research adipocytes adipose tissue caveolae obesity |
author_facet |
Lili Yue Theodore Mazzone |
author_sort |
Lili Yue |
title |
Endogenous adipocyte apolipoprotein E is colocalized with caveolin at the adipocyte plasma membrane |
title_short |
Endogenous adipocyte apolipoprotein E is colocalized with caveolin at the adipocyte plasma membrane |
title_full |
Endogenous adipocyte apolipoprotein E is colocalized with caveolin at the adipocyte plasma membrane |
title_fullStr |
Endogenous adipocyte apolipoprotein E is colocalized with caveolin at the adipocyte plasma membrane |
title_full_unstemmed |
Endogenous adipocyte apolipoprotein E is colocalized with caveolin at the adipocyte plasma membrane |
title_sort |
endogenous adipocyte apolipoprotein e is colocalized with caveolin at the adipocyte plasma membrane |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2011-03-01 |
description |
Apolipoprotein (apo)E is well established as a secreted protein that plays an important role in systemic lipoprotein metabolism and vascular wall homeostasis. Recently, endogenous expression of apoE in adipocytes has been shown to play an important role in adipocyte lipoprotein metabolism and gene expression consistent with a nonsecreted cellular itinerary for apoE. We designed studies to evaluate if adipocyte apoE was retained as a constituent protein in adipocytes and to identify a cellular retention compartment. Using confocal microscopy, coimmunoprecipitation, and sucrose density cellular fractionation, we establish that endogenous apoE shares a cellular itinerary with the constituent protein caveolin-1. Altering adipocyte caveolar number by modulating cellular cholesterol flux or altering caveolin expression regulates the distribution of cellular apoE between cytoplasmic and plasma membrane compartments. A mechanism for colocalization of apoE with caveolin was established by demonstrating a noncovalent interaction between an aromatic amino acid-enriched apoE N-terminal domain with the caveolin scaffolding domain. Absent apoE expression in adipocytes alters caveolar lipid composition. These observations provide evidence for an interaction between two proteins involved in cellular lipid metabolism in a cell specialized for lipid storage and flux, and rationalize a biological basis for the impact of adipocyte apoE expression on adipocyte lipoprotein metabolism. |
topic |
adipocytes adipose tissue caveolae obesity |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520409290 |
work_keys_str_mv |
AT liliyue endogenousadipocyteapolipoproteineiscolocalizedwithcaveolinattheadipocyteplasmamembrane AT theodoremazzone endogenousadipocyteapolipoproteineiscolocalizedwithcaveolinattheadipocyteplasmamembrane |
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1721504414724784128 |