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Cholesterol at the Endoplasmic Reticulum: Roles of the Sigma-1 Receptor Chaperone and Implications thereof in Human Diseases

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Book cover Cholesterol Binding and Cholesterol Transport Proteins:

Part of the book series: Subcellular Biochemistry ((SCBI,volume 51))

Abstract

Despite substantial data elucidating the roles of cholesterol in lipid rafts at the plasma membrane, the roles of cholesterol and related lipids in lipid raft microdomains at the level of subcellular membrane, such as the endoplasmic reticulum (ER) membrane, remain less understood. Growing evidence, however, begins to unveil the importance of cholesterol and lipids on the lipid raft at the ER membrane. A few ER proteins including the sigma-1 receptor chaperone were identified at lipid raft-like microdomains of the ER membrane. The sigma-1 receptor, which is highly expressed at a subdomain of ER membrane directly apposing mitochondria and known as the mitochondria-associated ER membrane or MAM, has been shown to associate with steroids as well as cholesterol. The sigma-1 receptor has been implicated in ER lipid metabolisms/transports, lipid raft reconstitution at the plasma membrane, trophic factor signalling, cellular differentiation, and cellular protection against β-amyloid-induced neurotoxicity. Recent studies on sigma-1 receptor chaperones and other ER proteins clearly suggest that cholesterol, in concert with those ER proteins, may regulate several important functions of the ER including folding, degradation, compartmentalization, and segregation of ER proteins, and the biosynthesis of sphingolipids.

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Abbreviations

ER:

endoplasmic reticulum

MAM:

mitochondria-associated ER membrane

SREBP:

sterol regulatory element binding protein

PHB:

prohibitin domain-containing

PrP:

prion protein

erlin:

ER lipid raft protein

IP3 receptors:

inositol 1,4,5-trisphosphate receptors

PtSer:

phosphatidylserine

PtEt:

phosphatidylethanolamine

SBDL:

sterol-binding domain-like

IAF:

iodo-azido fenpropimorph

NGF:

nerve growth factor

EGF:

epidermal growth factor

BDNF:

brain-derived neurotrophic factor

MAPK:

mitogen-activated protein kinase

NMDA:

N-methyl-D-aspartate

Hsp:

heat shock protein

BiP:

immunoglobulin binding protein

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Acknowledgement

This work is supported by Intramural Research Program, NIDA, NIH, DHHS.

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  1. Cellular Pathobiology Section, Cellular Neurobiology Research Branch, Intramural Research Program, National Institute on Drug Abuse, Department of Health and Human Services, National Institutes of Health, 333 Cassell Drive, Baltimore, MD, 21224, USA

    Teruo Hayashi & Tsung-Ping Su

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  1. Teruo Hayashi
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Correspondence to Teruo Hayashi or Tsung-Ping Su .

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    J. Robin Harris

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Hayashi, T., Su, TP. (2010). Cholesterol at the Endoplasmic Reticulum: Roles of the Sigma-1 Receptor Chaperone and Implications thereof in Human Diseases. In: Harris, J. (eds) Cholesterol Binding and Cholesterol Transport Proteins:. Subcellular Biochemistry, vol 51. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-8622-8_13

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