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Role of Syndecans in Lipid Metabolism and Human Diseases

  • Chapter
Lipids in Protein Misfolding

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 855))

Abstract

Syndecans are transmembrane heparan sulfate proteoglycans involved in the regulation of cell growth, differentiation, adhesion, neuronal development, and lipid metabolism. Syndecans are expressed in a tissue-specific manner to facilitate diverse cellular processes. As receptors and co-receptors, syndecans provide promising therapeutic targets that bind to a variety of physiologically important ligands. Negatively charged glycosaminoglycan chains of syndecans, located in the extracellular compartment, are critical for such binding. Functions of syndecans are as diverse as their ligands. For example, hepatic syndecan-1 mediates clearance of triglyceride-rich lipoproteins. Syndecan-2 promotes localization of Alzheimer’s amyloid Aβ peptide to the cell surface, which is proposed to contribute to amyloid plaque formation. Syndecan-3 helps co-localize the appetite-regulating melanocortin-4 receptor with its agonist, leading to an increased appetite. Finally, syndecan-4 initiates the capture of modified low-density lipoproteins by macrophages and thereby promotes the atheroma formation. We hypothesize that syndecan modifications such as desulfation of glycosaminoglycan chains may contribute to a wide range of diseases, from atherosclerosis to type 2 diabetes. At the same time, desulfated syndecans may have beneficial effects, as they can inhibit amyloid plaque formation or decrease the appetite. Despite considerable progress in understanding diverse functions of syndecans, the complex physiological roles of this intriguing family of proteoglycans are far from clear. Additional studies of syndecans may potentially help develop novel therapeutic approaches and diagnostic tools to alleviate complex human diseases such as cardiovascular and Alzheimer’s diseases.

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Abbreviations

AD:

Alzheimer’s disease

AgRP:

Agouti-related protein

apo:

Apolipoprotein

APP:

Amyloid-β precursor protein

Aβ:

Amyloid-β peptide

DPAB:

Dense peripheral actin bands

EG:

Endothelial glycocalyx

HDL:

High-density lipoproteins

HSPG:

Heparan sulfate proteoglycan

IDL:

Intermediate-density lipoproteins

LDL:

Low-density lipoproteins

MAP:

mitogen-activated protein kinase

MC4R:

Melanocortin-4 receptor

MMP:

Matrix metalloproteinase

PTK:

Protein tyrosine kinase

SULF2:

Heparan sulfate glucosamine-6-O-endosulfatase-2

TG:

Triacylglycerols

VLDL:

Very low-density lipoproteins

α-MSH:

α-melanocyte-stimulating anorexigenic hormone

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Acknowledgement

We are grateful Olga Gursky for her expert assistance and valuable comments. This study was supported by the Russian Science Foundation grant №14-14-00536 to O. V. G. and by the Russian Academy of Sciences (Molecular and Cell Biology program (grant 01201353567) to E. I. L.

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Authors and Affiliations

  1. Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia

    Elena I. Leonova & Oxana V. Galzitskaya

  2. Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia

    Elena I. Leonova

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  1. Elena I. Leonova
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Correspondence to Oxana V. Galzitskaya .

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  1. Dept. of Physiology and Biophysics, Boston University School of Medicine, Boston, Massachusetts, USA

    Olga Gursky

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Leonova, E.I., Galzitskaya, O.V. (2015). Role of Syndecans in Lipid Metabolism and Human Diseases. In: Gursky, O. (eds) Lipids in Protein Misfolding. Advances in Experimental Medicine and Biology, vol 855. Springer, Cham. https://doi.org/10.1007/978-3-319-17344-3_10

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