Proteomics, Glycomics, and Glycoproteomics of Matrisome Molecules

Raghunathan, Rekha; Sethi, Manveen K.; Klein, Joshua; Zaia, Joseph

doi:10.1074/mcp.r119.001543

Cited by 45 publications

(35 citation statements)

References 155 publications

(127 reference statements)

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“…The integration of proteomics, glycoproteomics and glycomics is proving to be a valuable approach for holistic characterization of glycoproteome regulation (44). Specifically, we show a switch in terminal di-galactosylation and sialylation linkages mediated by changes in glycosyltransferase/sialyltransferase expression.…”

Section: Discussionmentioning

confidence: 77%

Integrated Glycoproteomics Identifies a Role of N-Glycosylation and Galectin-1 on Myogenesis and Muscle Development

Blazev

Ashwood

Abrahams

et al. 2021

Molecular & Cellular Proteomics

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Many cell surface and secreted proteins are modified by the covalent addition of glycans that play an important role in the development of multicellular organisms. These glycan modifications enable communication between cells and the extracellular matrix via interactions with specific glycan-binding lectins and the regulation of receptor-mediated signaling. Aberrant protein glycosylation has been associated with the development of several muscular diseases suggesting essential glycan- and lectin-mediated functions in myogenesis and muscle development but our molecular understanding of the precise glycans, catalytic enzymes and lectins involved remain only partially understood. Here, we quantified dynamic remodeling of the membrane-associated proteome during a time-course of myogenesis in cell culture. We observed wide-spread changes in the abundance of several important lectins and enzymes facilitating glycan biosynthesis. Glycomics-based quantification of released N-linked glycans confirmed remodeling of the glycome consistent with the regulation of glycosyltransferases and glycosidases responsible for their formation including a previously unknown di-galactose-to-sialic acid switch supporting a functional role of these glycoepitopes in myogenesis. Furthermore, dynamic quantitative glycoproteomic analysis with multiplexed stable isotope labelling and analysis of enriched glycopeptides with multiple fragmentation approaches identified glycoproteins modified by these regulated glycans including several integrins and growth factor receptors. Myogenesis was also associated with the regulation of several lectins most notably the up-regulation of galectin-1 (LGALS1). CRISPR/Cas9-mediated deletion of Lgals1 inhibited differentiation and myotube formation suggesting an early functional role of galectin-1 in the myogenic program. Importantly, similar changes in N-glycosylation and the up-regulation of galectin-1 during postnatal skeletal muscle development were observed in mice. Treatment of new-born mice with recombinant adeno-associated viruses to overexpress galectin-1 in the musculature resulted in enhanced muscle mass. Our data form a valuable resource to further understand the glycobiology of myogenesis and will aid the development of intervention strategies to promote healthy muscle development or regeneration.

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Section: Discussionmentioning

confidence: 77%

Integrated Glycoproteomics Identifies a Role of N-Glycosylation and Galectin-1 on Myogenesis and Muscle Development

Blazev

Ashwood

Abrahams

et al. 2021

Molecular & Cellular Proteomics

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show abstract

“…Although there are only a few hundreds of glycoproteins in total, their highly complex glycosylation increases the number of theoretical protein morphology by several orders of magnitude 9 . Many cell surface and extracellular matrix-related proteins become glycosylated through secretory pathways, thereby regulating their adhesion interactions, physical and chemical properties, and diversifying their functions 10 .…”

Section: Resultsmentioning

confidence: 99%

N-glycoproteomic Profiling Revealing New Coronavirus Therapeutic Targets That Maybe Involved in Cepharanthine’s Intervention

Tian

et al. 2020

Preprint

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N-glycosylation is an important post-translational modification involved in protein folding, signal transduction, extracellular matrix organization and immune response. Evidence showed that glycosylated SARS-CoV-2 Spike protein may be a potential target in viral pathogenesis and drug/vaccine design. To investigate the mechanism of coronavirus infestation and drug targets from glycosylation perspective, we constructed a SARS-CoV-2 cellular model using GX_P2V-infected VeroE6 cells to study the effects of GX_P2V on glycoproteins in presence or absence of Cepharanthine (CEP) through N-glycoproteomics profiling. The results showed that coronavirus GX_P2V could cause aberrant protein glycosylation, whereas CEP can partially maintain GX_P2V-induced aberrant glycoproteins at homeostasis. Further study revealed that proteins LAMB1 and FN1 were pivotal in counteracting coronavirus-induced aberrant protein glycosylation by CEP. Furthermore, CEP can dramatically regulate the glycosylation of viral proteins S, M and N. Our results suggest that despite the strong anti-coronavirus effects of CEP, drug combinations need be considered to achieve optimal therapeutic strategies.

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“…The integration of proteomics, glycoproteomics and glycomics is proving to be a valuable approach for holistic characterization of glycoproteome regulation (43). Therefore, galectins have been primarily studied in the context of extracellular lattice formation however, there is growing evidence to suggest galectins may regulate intracellular signaling via lysosomal trafficking (69).…”

Section: Discussionmentioning

confidence: 99%

Integrated glycoproteomics identifies a role ofN-glycosylation and galectin-1 on myogenesis and muscle development

Blazev

Ashwood

Abrahams

et al. 2020

Preprint

View full text Add to dashboard Cite

ABSTRACTMany cell surface and secreted proteins are modified by the covalent addition of glycans that play an important role in the development of multicellular organisms. These glycan modifications enable communication between cells and the extracellular matrix via interactions with specific glycan-binding lectins and the regulation of receptor-mediated signaling. Aberrant protein glycosylation has been associated with the development of several muscular diseases suggesting essential glycan- and lectin-mediated functions in myogenesis and muscle development but our molecular understanding of the precise glycans, catalytic enzymes and lectins involved remain only partially understood. Here, we quantified dynamic remodeling of the membrane-associated proteome during a time-course of myogenesis in cell culture. We observed wide-spread changes in the abundance of several important lectins and enzymes facilitating glycan biosynthesis. Glycomics-based quantification of released N-linked glycans confirmed remodeling of the glycome consistent with the regulation of glycosyltransferases and glycosidases responsible for their formation including a previously unknown di-galactose-to-sialic acid switch supporting a functional role of these glycoepitopes in myogenesis. Furthermore, dynamic quantitative glycoproteomic analysis with multiplexed stable isotope labelling and analysis of enriched glycopeptides with multiple fragmentation approaches identified glycoproteins modified by these regulated glycans including several integrins and growth factor receptors. Myogenesis was also associated with the regulation of several lectins most notably the up-regulation of galectin-1 (LGALS1). CRISPR/Cas9-mediated deletion of Lgals1 inhibited differentiation and myotube formation suggesting an early functional role of galectin-1 in the myogenic program. Importantly, similar changes in N-glycosylation and the up-regulation of galectin-1 during postnatal skeletal muscle development were observed in mice. Treatment of new-born mice with recombinant adeno-associated viruses to overexpress galectin-1 in the musculature resulted in enhanced muscle mass. Our data form a valuable resource to further understand the glycobiology of myogenesis and will aid the development of intervention strategies to promote healthy muscle development or regeneration.

show abstract

Proteomics, Glycomics, and Glycoproteomics of Matrisome Molecules

Cited by 45 publications

References 155 publications

Integrated Glycoproteomics Identifies a Role of N-Glycosylation and Galectin-1 on Myogenesis and Muscle Development

Integrated Glycoproteomics Identifies a Role of N-Glycosylation and Galectin-1 on Myogenesis and Muscle Development

N-glycoproteomic Profiling Revealing New Coronavirus Therapeutic Targets That Maybe Involved in Cepharanthine’s Intervention

Integrated glycoproteomics identifies a role ofN-glycosylation and galectin-1 on myogenesis and muscle development

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