Unraveling the Mechanism of Protein N-Glycosylation

Yan, Aixin; Lennarz, William J.

doi:10.1074/jbc.r400036200

Cited by 189 publications

(124 citation statements)

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“…The deduced mouse myonectin protein consists of five domains: a signal peptide for secretion, an N-terminal domain-1 (NTD1), a short collagen domain with six Gly-X-Y repeats, an N-terminal domain-2 (NTD2), and a C-terminal C1q/TNF-like domain. This protein consists of 340 amino acids and contains four Cys residues and four potential N-linked glycosylation sites that conform to the consensus sequence N-X-(Ser/Thr) (34). The 7.8-kb mouse myonectin gene is located on chromosome 1 (contig NC_000002.11) and contains eight exons.…”

Section: Resultsmentioning

confidence: 99%

Myonectin (CTRP15), a Novel Myokine That Links Skeletal Muscle to Systemic Lipid Homeostasis

Seldin

Peterson

Byerly

et al. 2012

Journal of Biological Chemistry

327

406

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Background: Skeletal muscle-derived myokines modulate metabolic, inflammatory, and other processes. Results: Myonectin, a novel myokine whose expression and circulating levels are regulated by diet, metabolic state, and exercise, functions to control lipid metabolism. Conclusion: Myonectin is a potential nutrient-responsive metabolic regulator secreted by muscle. Significance: Myonectin links muscle to systemic lipid metabolism via its action on adipocytes and hepatocytes, providing insight into complex tissue cross-talk.

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Section: Resultsmentioning

confidence: 99%

Myonectin (CTRP15), a Novel Myokine That Links Skeletal Muscle to Systemic Lipid Homeostasis

Seldin

Peterson

Byerly

et al. 2012

Journal of Biological Chemistry

327

406

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“…In contrast to the glycosaminoglycans of proteoglycans, the carbohydrate moieties of a typical glycoprotein are smaller and more structurally diverse (Ohtsubo and Marth, 2006). The two main types of carbohydrate-protein conjugation in glycoproteins are N-glycosylation (Yan and Lennarz, 2005) and O-glycosylation (Peter-Katalinic, 2005). O-linked carbohydrate bonding occurs through serine or threonine, and N-glycosidic linkage to asparagine residues (Ohtsubo and Marth, 2006).…”

Section: Introductionmentioning

confidence: 99%

Lectin-based proteomic profiling of aged skeletal muscle: Decreased pyruvate kinase isozyme M1 exhibits drastically increased levels of N-glycosylation

O’Connell

Doran

Gannon

et al. 2008

European Journal of Cell Biology

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Since various neuromuscular diseases are associated with abnormal glycosylation, it was of interest to determine whether this key post-translational modification is also altered in aged skeletal muscle. Lectins represent highly versatile carbohydrate-binding proteins that are routinely employed for the characterization of glycoproteins. Here, we used the lectin wheat germ agglutinin (WGA) for the proteomic profiling of senescent fibers. WGA labeling of the soluble proteome from 3-month-versus 30-month-old rat gastrocnemius muscle, following two-dimensional gel electrophoretic separation, resulted in the identification of 13 distinct protein species. Analysis of WGA binding levels, in conjunction with mass spectrometric fingerprinting, revealed that one isoform of a major metabolic muscle protein exhibited a drastic alteration in the content of sialic acid and N-acetylglucosaminyl sugar residues. Pyruvate kinase isoform M1 with protein accession number gi|16757994|, exhibiting a pI of 6.6 and an apparent molecular mass of 57.8 kDa, showed a six fold increase in N-glycosylation and a three fold decrease in protein expression. In contrast to comparable levels of N-glycosylated proteins in young adult versus senescent muscle, as judged by fluoresceinconjugated WGA labeling of transverse muscle cryosections, staining with antibodies to the M1 isoform of pyruvate kinase showed reduced expression of this cytosolic element. Furthermore, activity assays demonstrated a reduced activity of this glycolytic enzyme in senescent muscle. This agrees with the idea that abnormal post-translational modifications in key metabolic enzymes may be involved in the conversion of aged muscle to slower twitch patterns and a drastic shift to more aerobic-oxidative metabolism.

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“…The enzyme involved in the transfer reaction (the oligosaccharyltransferase or OST) appeared to be a membrane-bound complex that was closely associated to the translocon and was formed in Saccharomyces cerevisiae by eight subunits, five of which appeared to be essential for viability of the microorganism (4)(5)(6). Several lines of evidence indicate that one of the essential proteins (Stt3p) is the catalytic subunit and is actually responsible for the transfer of the glycan.…”

Section: N-glycosylation ͉ Saccharomyces Cerevisiae ͉ Trypanosoma Cruzimentioning

confidence: 99%

Preferential transfer of the complete glycan is determined by the oligosaccharyltransferase complex and not by the catalytic subunit

Castro

Movsichoff

Parodi

2006

Proc. Natl. Acad. Sci. U.S.A.

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Most eukaryotic cells show a strong preference for the transfer in vivo and in vitro of the largest dolichol-P-P-linked glycan (Glc 3Man9GlcNAc2) to protein chains over that of biosynthetic intermediates that lack the full complement of glucose units. The oligosaccharyltransferase (OST) is a multimeric complex containing eight different proteins, one of which (Stt3p) is the catalytic subunit. Trypanosomatid protozoa lack an OST complex and express only this last protein. Contrary to the OST complex from most eukaryotic cells, the Stt3p subunit of these parasites transfers in cell-free assays glycans with Man 7-9GlcNAc2 and Glc 1-3Man9GlcNAc2 compositions at the same rate. We have replaced Saccharomyces cerevisiae Stt3p by the Trypanosoma cruzi homologue and found that the complex that is formed preferentially transfers the complete glycan both in vivo and in vitro. Thus, preference for Glc 3Man9GlcNAc2 is a feature that is determined by the complex and not by the catalytic subunit. N-glycosylation ͉ Saccharomyces cerevisiae ͉ Trypanosoma cruzi

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Unraveling the Mechanism of Protein N-Glycosylation

Cited by 189 publications

References 50 publications

Myonectin (CTRP15), a Novel Myokine That Links Skeletal Muscle to Systemic Lipid Homeostasis

Myonectin (CTRP15), a Novel Myokine That Links Skeletal Muscle to Systemic Lipid Homeostasis

Lectin-based proteomic profiling of aged skeletal muscle: Decreased pyruvate kinase isozyme M1 exhibits drastically increased levels of N-glycosylation

Preferential transfer of the complete glycan is determined by the oligosaccharyltransferase complex and not by the catalytic subunit

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