Abstract
The ECM is a complex molecular network that surrounds all cells and consists of proteins, glycoproteins, hyaluronan, glycosaminoglycans (GAGs), and proteoglycans (PGs). GAGs and PGs play vital roles in ECM-related processes such as cell migration, proliferation, adhesion, and differentiation. Among the omics technologies, including genomics, transcriptomics, and proteomics, glycomics is the least mature. Over the past two decades, with efforts from glycoscientists around world, and the advent of new glyco-techonologies, databases, tools, and methods, much progress has been made. Now, the focus is to integrate proteomics and glycomics domains in a new platform to analyze and characterize biomolecule classes and define their structural and functional roles. Towards this end, we have developed approaches that integrate analysis of GAGs and proteins towards an end goal of elucidating pathophysiological mechanisms to inform development of disease therapies and regenerative medicine. In this chapter, we provide a historical overview of our groups’ methods for glycomics, glycoproteomics, and proteomics of key ECM constituents, i.e., GAGs and PGs, as reported over the past decade.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
Abbreviations
- CE:
-
Capillary electrophoresis
- CS:
-
Chondroitin sulfate
- DS:
-
Dermatan Sulfate
- ECM:
-
Extracellular matrix
- GAGs:
-
Glycosaminoglycans
- GalNAc:
-
N-acetylgalactosamine
- GlcA:
-
Glucuronic acid
- GlcNAc:
-
N-acetylglucosamine
- HA:
-
Hyaluronic acid
- HEP:
-
Heparin
- HILIC:
-
Hydrophilic interaction chromatography
- HS:
-
Heparan sulfate
- IdoA:
-
Iduronic acid
- IMS:
-
Imaging mass spectrometry
- IPRP:
-
Ion-pair reversed-phase chromatography
- KS:
-
Keratan sulfate
- LC:
-
Liquid chromatography
- LIF:
-
Laser-induced fluorescence
- MALDI:
-
Matrix-assisted laser desorption/ionization
- MS:
-
Mass spectrometry
- MS/MS:
-
Tandem mass spectrometry
- MWCO:
-
Molecular weight cut-off filters
- PGs:
-
Proteoglycans
- PNNs:
-
Perineuronal nets
- PTMs:
-
Post-translational modifications
- SEC:
-
Size exclusion chromatography
- TOF:
-
Time-of-flight
References
Afratis N, Gialeli C, Nikitovic D, Tsegenidis T, Karousou E, Theocharis AD, Pavao MS, Tzanakakis GN, Karamanos NK (2012) Glycosaminoglycans: key players in cancer cell biology and treatment. FEBS J 279:1177–1197
Apweiler R, Hermjakob H, Sharon N (1999) On the frequency of protein glycosylation, as deduced from analysis of the SWISS-PROT database. Biochim Biophys Acta 1473:4–8
Bielik AM, Zaia J (2010) Extraction of chondroitin/dermatan sulfate glycosaminoglycans from connective tissue for mass spectrometric analysis. Methods Mol Biol 600:215–225
Bielik AM, Zaia J (2011) Multistage tandem mass spectrometry of chondroitin sulfate and dermatan sulfate. Int J Mass Spectrom 305:131–137
Bodet PE, Salard I, Przybylski C, Gonnet F, Gomila C, Ausseil J, Daniel R (2017) Efficient recovery of glycosaminoglycan oligosaccharides from polyacrylamide gel electrophoresis combined with mass spectrometry analysis. Anal Bioanal Chem 409:1257–1269
Bowman MJ, Zaia J (2010) Comparative glycomics using a tetraplex stable-isotope coded tag. Anal Chem 82:3023–3031
Byron A, Humphries JD, Humphries MJ (2013) Defining the extracellular matrix using proteomics. Int J Exp Pathol 94:75–92
Calvano CD, Zambonin CG, Jensen ON (2008) Assessment of lectin and HILIC based enrichment protocols for characterization of serum glycoproteins by mass spectrometry. J Proteome 71:304–317
Chang CW, Dalgliesh AJ, Lopez JE, Griffiths LG (2016) Cardiac extracellular matrix proteomics: challenges, techniques, and clinical implications. Proteomics Clin Appl 10:39–50
Chen J, Kawamura T, Sethi MK, Zaia J, Repunte-Canonigo V, Sanna PP (2017) Heparan sulfate: resilience factor and therapeutic target for cocaine abuse. Sci Rep 7:13931
Conrad HE (1997) Heparin-binding proteins. Elsevier
Donovan LE, Higginbotham L, Dammer EB, Gearing M, Rees HD, Xia Q, Duong DM, Seyfried NT, Lah JJ, Levey AI (2012) Analysis of a membrane-enriched proteome from postmortem human brain tissue in Alzheimer’s disease. Proteomics Clin Appl 6:201–211
Drake RR, Powers TW, Jones EE, Bruner E, Mehta AS, Angel PM (2017) MALDI mass spectrometry imaging of N-linked glycans in cancer tissues. Adv Cancer Res 134:85–116
Drake RR, Powers TW, Norris-Caneda K, Mehta AS, Angel PM (2018a) In situ imaging of N-glycans by MALDI imaging mass spectrometry of fresh or formalin-fixed paraffin-embedded tissue. Curr Protocols Protein Sci 94:e68
Drake RR, West CA, Mehta AS, Angel PM (2018b) MALDI mass spectrometry imaging of N-linked glycans in tissues. Adv Exp Med Biol 1104:59–76
Funderburgh JL (2000) MINI REVIEW Keratan sulfate: structure, biosynthesis, and function. Glycobiology 10:951–958
Gill VL, Aich U, Rao S, Pohl C, Zaia J (2013) Disaccharide analysis of glycosaminoglycans using hydrophilic interaction chromatography and mass spectrometry. Anal Chem 85:1138–1145
Goddard ET, Hill RC, Barrett A, Betts C, Guo Q, Maller O, Borges VF, Hansen KC, Schedin P (2016) Quantitative extracellular matrix proteomics to study mammary and liver tissue microenvironments. Int J Biochem Cell Biol 81:223–232
Henriksen J, Ringborg LH, Roepstorrf P (2004) On-line size-exclusion chromatography/mass spectrometry of low molecular mass heparin. J Mass Spectrom 39:1305–1312
Hill RC, Calle EA, Dzieciatkowska M, Niklason LE, Hansen KC (2015) Quantification of extracellular matrix proteins from a rat lung scaffold to provide a molecular readout for tissue engineering. Mol Cell Proteomics 14:961–973
Hitchcock AM, Costello CE, Zaia J (2006) Glycoform quantification of chondroitin/dermatan sulfate using a liquid chromatography-tandem mass spectrometry platform. Biochemistry 45:2350–2361
Hitchcock AM, Bowman MJ, Staples GO, Zaia J (2008a) Improved workup for glycosaminoglycan disaccharide analysis using CE with LIF detection. Electrophoresis 29:4538–4548
Hitchcock AM, Yates KE, Costello CE, Zaia J (2008b) Comparative glycomics of connective tissue glycosaminoglycans. Proteomics 8:1384–1397
Hondius DC, van Nierop P, Li KW, Hoozemans JJ, van der Schors RC, van Haastert ES, van der Vies SM, Rozemuller AJ, Smit AB (2016) Profiling the human hippocampal proteome at all pathologic stages of Alzheimer’s disease. Alzheimer’s Dementia 12:654–668
Huang Y, Shi X, Yu X, Leymarie N, Staples GO, Yin H, Killeen K, Zaia J (2011) Improved liquid chromatography-MS/MS of heparan sulfate oligosaccharides via chip-based pulsed makeup flow. Anal Chem 83:8222–8229
Iozzo RV, Schaefer L (2015) Proteoglycan form and function: a comprehensive nomenclature of proteoglycans. Mat Biol 42:11–55
Jacobsen A, Shi X, Shao C, Eysturskardelta J, Mikalsen SO, Zaia J (2019) Characterization of glycosaminoglycans in gaping and intact connective tissues of farmed Atlantic Salmon (Salmo salar) fillets by mass spectrometry. ACS Omega 4:15337–15347
Ji IJ, Hua S, Shin DH, Seo N, Hwang JY, Jang IS, Kang MG, Choi JS, An HJ (2015) Spatially-resolved exploration of the mouse brain glycome by tissue glyco-capture (TGC) and nano-LC/MS. Anal Chem 87:2869–2877
Kailemia MJ, Ruhaak LR, Lebrilla CB, Amster IJ (2014) Oligosaccharide analysis by mass spectrometry: a review of recent developments. Anal Chem 86:196–212
Khatri K, Staples GO, Leymarie N, Leon DR, Turiak L, Huang Y, Yip S, Hu H, Heckendorf CF, Zaia J (2014) Confident assignment of site-specific glycosylation in complex glycoproteins in a single step. J Proteome Res 13:4347–4355
Khatri K, Klein JA, White MR, Grant OC, Leymarie N, Woods RJ, Hartshorn KL, Zaia J (2016) Integrated omics and computational glycobiology reveal structural basis for influenza A virus glycan microheterogeneity and host interactions. Mol Cell Proteomics 15:1895–1912
Kjellen L, Lindahl U (1991) Proteoglycans: structures and interactions. Annu Rev Biochem 60:443–475
Klein JA, Meng L, Zaia J (2018) Deep sequencing of complex proteoglycans: a novel strategy for high coverage and site-specific identification of glycosaminoglycan-linked peptides. Mol Cell Proteomics 17:1578–1590
Laremore TN, Linhardt RJ (2007) Improved matrix-assisted laser desorption/ionization mass spectrometric detection of glycosaminoglycan disaccharides as cesium salts. Rapid Commun Mass Spectrom 21:1315–1320
Leymarie N, McComb ME, Naimy H, Staples GO, Zaia J (2012) Differential characterization and classification of tissue specific glycosaminoglycans by tandem mass spectrometry and statistical methods. Int J Mass Spectrom 312:144–154
Lindahl U, Couchman J, Kimata K, Esko JD (2015) Proteoglycans and sulfated glycosaminoglycans. In: Varki A, Cummings RD, Esko JD, Stanley P, Hart GW, Aebi M, Darvill AG, Kinoshita T, Packer NH et al (eds) Essentials of glycobiology. Cold Spring Harbor, New York, pp 207–221
Lindsey ML, Hall ME, Harmancey R, Ma Y (2016) Adapting extracellular matrix proteomics for clinical studies on cardiac remodeling post-myocardial infarction. Clin Proteomics 13:19
Liu H, Joshi A, Chopra P, Liu L, Boons G-J, Sharp JS (2019) Salt-free fractionation of complex isomeric mixtures of glycosaminoglycan oligosaccharides compatible with ESI-MS and microarray analysis. Sci Rep 9:16566
Luo Q, Rejtar T, Wu S-L, Karger BL (2009) Hydrophilic interaction 10μm I.D. porous layer open tubular columns for ultratrace glycan analysis by liquid chromatography–mass spectrometry. J Chromatogr A 1216:1223–1231
Martin GR, Kleinman HK, Terranova VP, Ledbetter S, Hassell JR (1984) The regulation of basement membrane formation and cell-matrix interactions by defined supramolecular complexes. CIBA Found Symp 108:197–212
Mauko L, Pelzing M, Dolman S, Nordborg A, Lacher NA, Haddad PR, Hilder EF (2011) Zwitterionic-type hydrophilic interaction nano-liquid chromatography of complex and high mannose glycans coupled with electrospray ionisation high resolution time of flight mass spectrometry. J Chromatogr A 1218:6419–6425
Muir EM, Adcock KH, Morgenstern DA, Clayton R, von Stillfried N, Rhodes K, Ellis C, Fawcett JW, Rogers JH (2002) Matrix metalloproteases and their inhibitors are produced by overlapping populations of activated astrocytes. Brain Res Mol Brain Res 100:103–117
Naba A, Clauser KR, Hoersch S, Liu H, Carr SA, Hynes RO (2012) The matrisome: in silico definition and in vivo characterization by proteomics of normal and tumor extracellular matrices. Mol Cell Proteomics 11:M111.014647
Naba A, Clauser KR, Hynes RO (2015) Enrichment of extracellular matrix proteins from tissues and digestion into peptides for mass spectrometry analysis. J Visual Exp: JoVE e53057
Naba A, Pearce OMT, Del Rosario A, Ma D, Ding H, Rajeeve V, Cutillas PR, Balkwill FR, Hynes RO (2017) Characterization of the extracellular matrix of normal and diseased tissues using proteomics. J Proteome Res 16:3083–3091
Raghunathan R, Polinski NK, Klein JA, Hogan JD, Shao C, Khatri K, Leon D, McComb ME, Manfredsson FP, Sortwell CE et al (2018) Glycomic and proteomic changes in aging brain nigrostriatal pathway. Mol Cell Proteomics 17:1778–1787
Raghunathan R, Sethi MK, Klein JA, Zaia J (2019a) Proteomics, glycomics, and glycoproteomics of matrisome molecules. Mol Cell Proteomics
Raghunathan R, Sethi MK, Zaia J (2019b) On-slide tissue digestion for mass spectrometry based glycomic and proteomic profiling. MethodsX 6:2329–2347
Rivera S, Khrestchatisky M, Kaczmarek L, Rosenberg GA, Jaworski DM (2010) Metzincin proteases and their inhibitors: foes or friends in nervous system physiology? J Neurosci Off J Soc Neurosci 30:15337–15357
Ruhaak LR, Huhn C, Waterreus W-J, de Boer AR, Neusüss C, Hokke CH, Deelder AM, Wuhrer M (2008) Hydrophilic interaction chromatography-based high-throughput sample preparation method for N-glycan analysis from total human plasma glycoproteins. Anal Chem 80:6119–6126
Sethi MK, Zaia J (2017) Extracellular matrix proteomics in schizophrenia and Alzheimer’s disease. Anal Bioanal Chem 409:379–394
Shao C, Shi X, Phillips JJ, Zaia J (2013a) Mass spectral profiling of glycosaminoglycans from histological tissue surfaces. Anal Chem 85:10984–10991
Shao C, Shi X, White M, Huang Y, Hartshorn K, Zaia J (2013b) Comparative glycomics of leukocyte glycosaminoglycans. FEBS J 280:2447–2461
Shao X, Taha IN, Clauser KR, Gao Y, Naba A (2019) MatrisomeDB: the ECM-protein knowledge database. Nucleic Acids Res 48:D1136–D1144
Shi X, Huang Y, Mao Y, Naimy H, Zaia J (2012) Tandem mass spectrometry of heparan sulfate negative ions: sulfate loss patterns and chemical modification methods for improvement of product ion profiles. J Am Soc Mass Spectrom 23:1498–1511
Solakyildirim K (2019) Recent advances in glycosaminoglycan analysis by various mass spectrometry techniques. Anal Bioanal Chem 411:3731–3741
Staples GO, Zaia J (2011) Analysis of glycosaminoglycans using mass spectrometry. Curr Proteomics 8:325–336
Staples GO, Bowman MJ, Costello CE, Hitchcock AM, Lau JM, Leymarie N, Miller C, Naimy H, Shi X, Zaia J (2009) A chip-based amide-HILIC LC/MS platform for glycosaminoglycan glycomics profiling. Proteomics 9:686–695
Staples GO, Naimy H, Yin H, Kileen K, Kraiczek K, Costello CE, Zaia J (2010) Improved hydrophilic interaction chromatography LC/MS of heparinoids using a chip with postcolumn makeup flow. Anal Chem 82:516–522
Sykova E, Nicholson C (2008) Diffusion in brain extracellular space. Physiol Rev 88:1277–1340
Turiak L, Shao C, Meng L, Khatri K, Leymarie N, Wang Q, Pantazopoulos H, Leon DR, Zaia J (2014) Workflow for combined proteomics and glycomics profiling from histological tissues. Anal Chem 86:9670–9678
Turnbull JE, Hopwood JJ, Gallagher JT (1999) A strategy for rapid sequencing of heparan sulfate and heparin saccharides. Proc Natl Acad Sci U S A 96:2698–2703
Turnbull JE, Miller RL, Ahmed Y, Puvirajesinghe TM, Guimond SE (2010) Glycomics profiling of heparan sulfate structure and activity. Methods Enzymol 480:65–85
Venkataraman G, Shriver Z, Raman R, Sasisekharan R (1999) Sequencing complex polysaccharides. Science 286:537–542
Wang Z, Zhang F, Dordick JS, Linhardt RJ (2012) Molecular mass characterization of glycosaminoglycans with different degrees of sulfation in bioengineered heparin process by size exclusion chromatography. Curr Anal Chem 8:506–511
Wisniewski JR (2016) Quantitative evaluation of filter aided sample preparation (FASP) and multienzyme digestion FASP protocols. Anal Chem 88:5438–5443
Wiśniewski JR, Zougman A, Nagaraj N, Mann M (2009) Universal sample preparation method for proteome analysis. Nat Methods 6:359
Wohlgemuth J, Karas M, Eichhorn T, Hendriks R, Andrecht S (2009) Quantitative site-specific analysis of protein glycosylation by LC-MS using different glycopeptide-enrichment strategies. Anal Biochem 395:178–188
Zaia J (2005) Principles of mass spectrometry of glycosaminoglycans. J Biomacromol Mass Spectrom 1:3–36
Zaia J (2008) Mass spectrometry and the emerging field of glycomics. Chem Biol 15:881–892
Zaia J (2009) On-line separations combined with MS for analysis of glycosaminoglycans. Mass Spectrom Rev 28:254–272
Zauner G, Koeleman CAM, Deelder AM, Wuhrer M (2010) Protein glycosylation analysis by HILIC-LC-MS of Proteinase K-generated N- and O-glycopeptides. J Sep Sci 33:903–910
Zauner G, Deelder AM, Wuhrer M (2011) Recent advances in hydrophilic interaction liquid chromatography (HILIC) for structural glycomics. Electrophoresis 32:3456–3466
Acknowledgements
This work was supported by NIH grants P41GM104602, R01MH105608, and R01GM133963.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Sethi, M.K., Zaia, J. (2020). Historical Overview of Integrated GAG-omics and Proteomics. In: Ricard-Blum, S. (eds) Extracellular Matrix Omics. Biology of Extracellular Matrix, vol 7. Springer, Cham. https://doi.org/10.1007/978-3-030-58330-9_5
Download citation
DOI: https://doi.org/10.1007/978-3-030-58330-9_5
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-58329-3
Online ISBN: 978-3-030-58330-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)