Characterization of C. elegans Chondroitin Proteoglycans and Their Large Functional and Structural Heterogeneity; Evolutionary Aspects on Structural Differences Between Humans and the Nematode

Noborn, Fredrik; Larson, Göran

doi:10.1007/5584_2020_485

Cited by 8 publications

(4 citation statements)

References 98 publications

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“…Furthermore, the strict conservation of the glycosylation site in CgA in three different species, and the GAG glycosylation of CgA in various human tissues (beta cells, CSF and urine), indicates the importance of this GAG structure for protein function. Notably, genes encoding HSPG core proteins typically display a high degree of conservation throughout evolution ( Noborn and Larson 2020 ). For instance, the recently identified HS site on the neurexin-1 gene is conserved from zebrafish to human ( Zhang et al.…”

Section: Discussionmentioning

confidence: 99%

Proteoglycan profiling of human, rat and mouse insulin-secreting cells

et al. 2021

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Proteoglycans (PGs) are proteins with glycosaminoglycan (GAG) chains, such as chondroitin sulfate (CS) or heparan sulfate (HS), attached to serine residues. We have earlier shown that prohormones can carry CS, constituting a novel class of PGs. The mapping of GAG modifications of proteins in endocrine cells may thus assist us in delineating possible roles of PGs in endocrine cellular physiology. With this aim, we applied a glycoproteomic approach to identify PGs, their GAG chains and their attachment sites in insulin-secreting cells. Glycopeptides carrying GAG chains were enriched from human pancreatic islets, rat (INS-1 832/13) and mouse (MIN6, NIT-1) insulinoma cell lines by ion exchange chromatography, depolymerized with GAG lyases, and analyzed by nanoflow liquid chromatography–tandem mass spectrometry (nLC-MS/MS). We identified CS modifications of chromogranin-A (CgA), islet amyloid polypeptide, secretogranin-1 and secretogranin-2, immunoglobulin superfamily member 10, and protein AMBP. Additionally, we identified two HS-modified prohormones (CgA and secretogranin-1), which was surprising, as prohormones are not typically regarded as HSPGs. For CgA, the glycosylation site carried either CS or HS, making it a so-called hybrid site. Additional HS sites were found on syndecan-1, syndecan-4, nerurexin-2, protein NDNF, and testican-1. These results demonstrate that several prohormones, and other constituents of the insulin-secreting cells are PGs. Cell-targeted mapping of the GAG glycoproteome forms an important basis for better understanding of endocrine cellular physiology, and the novel CS and HS sites presented here provide important knowledge for future studies.

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Section: Discussionmentioning

confidence: 99%

Proteoglycan profiling of human, rat and mouse insulin-secreting cells

et al. 2021

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“…New CSPGs have been identified in human urine and cerebrospinal fluid, including five prohormones (cholecystokinin, chromogranin A, neuropeptide W, secretogranins 1 and 3) [99]. Additional CSPGs and HSPGs were identified in mammalian insulin-secreted cells (e.g., the HSPGs and prohormones chromogranin A and secretogranin-1) [100], in Caenorhabditis elegans (15 novel CSPGs) [101], and in Drosophila (Windpipe, a novel membrane CSPG) [102]).…”

Section: The Linkage Region Of Gags To Core Proteinsmentioning

confidence: 99%

A biological guide to glycosaminoglycans: current perspectives and pending questions

Ricard‐Blum,

Vivès,

Schaefer

et al. 2024

The FEBS Journal

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Mammalian glycosaminoglycans (GAGs), except hyaluronan (HA), are sulfated polysaccharides that are covalently attached to core proteins to form proteoglycans (PGs). This article summarizes key biological findings for the most widespread GAGs, namely HA, chondroitin sulfate/dermatan sulfate (CS/DS), keratan sulfate (KS), and heparan sulfate (HS). It focuses on the major processes that remain to be deciphered to get a comprehensive view of the mechanisms mediating GAG biological functions. They include the regulation of GAG biosynthesis and postsynthetic modifications in heparin (HP) and HS, the composition, heterogeneity, and function of the tetrasaccharide linkage region and its role in disease, the functional characterization of the new PGs recently identified by glycoproteomics, the selectivity of interactions mediated by GAG chains, the display of GAG chains and PGs at the cell surface and their impact on the availability and activity of soluble ligands, and on their move through the glycocalyx layer to reach their receptors, the human GAG profile in health and disease, the roles of GAGs and particular PGs (syndecans, decorin, and biglycan) involved in cancer, inflammation, and fibrosis, the possible use of GAGs and PGs as disease biomarkers, and the design of inhibitors targeting GAG biosynthetic enzymes and GAG–protein interactions to develop novel therapeutic approaches.

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“…Until recently, C. elegans was known to express nine Chn/CS-PGs dissimilar to vertebrate CS-PGs. A recent glycoproteomic study identified 15 additional CPGs in C. elegans and three of these were homologous to human proteins, thus selected CS-PG core proteins appear conserved throughout evolution ( Noborn and Larson, 2021 ). Bioinformatic analysis of primary amino acid sequence data identified a broad range of functional domains in these C. elegans PGs, thus specific PG core protein mediated functional properties appeared to have evolved early in metazoan evolution.…”

Section: Developmental Animal Models Used To Examine Neural Development and Regulation In A Whole Organism Environmentmentioning

confidence: 99%

Neural Tissue Homeostasis and Repair Is Regulated via CS and DS Proteoglycan Motifs

Hayes

Melrose

2021

Front. Cell Dev. Biol.

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Chondroitin sulfate (CS) is the most abundant and widely distributed glycosaminoglycan (GAG) in the human body. As a component of proteoglycans (PGs) it has numerous roles in matrix stabilization and cellular regulation. This chapter highlights the roles of CS and CS-PGs in the central and peripheral nervous systems (CNS/PNS). CS has specific cell regulatory roles that control tissue function and homeostasis. The CNS/PNS contains a diverse range of CS-PGs which direct the development of embryonic neural axonal networks, and the responses of neural cell populations in mature tissues to traumatic injury. Following brain trauma and spinal cord injury, a stabilizing CS-PG-rich scar tissue is laid down at the defect site to protect neural tissues, which are amongst the softest tissues of the human body. Unfortunately, the CS concentrated in gliotic scars also inhibits neural outgrowth and functional recovery. CS has well known inhibitory properties over neural behavior, and animal models of CNS/PNS injury have demonstrated that selective degradation of CS using chondroitinase improves neuronal functional recovery. CS-PGs are present diffusely in the CNS but also form denser regions of extracellular matrix termed perineuronal nets which surround neurons. Hyaluronan is immobilized in hyalectan CS-PG aggregates in these perineural structures, which provide neural protection, synapse, and neural plasticity, and have roles in memory and cognitive learning. Despite the generally inhibitory cues delivered by CS-A and CS-C, some CS-PGs containing highly charged CS disaccharides (CS-D, CS-E) or dermatan sulfate (DS) disaccharides that promote neural outgrowth and functional recovery. CS/DS thus has varied cell regulatory properties and structural ECM supportive roles in the CNS/PNS depending on the glycoform present and its location in tissue niches and specific cellular contexts. Studies on the fruit fly, Drosophila melanogaster and the nematode Caenorhabditis elegans have provided insightful information on neural interconnectivity and the role of the ECM and its PGs in neural development and in tissue morphogenesis in a whole organism environment.

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Characterization of C. elegans Chondroitin Proteoglycans and Their Large Functional and Structural Heterogeneity; Evolutionary Aspects on Structural Differences Between Humans and the Nematode

Cited by 8 publications

References 98 publications

Proteoglycan profiling of human, rat and mouse insulin-secreting cells

Proteoglycan profiling of human, rat and mouse insulin-secreting cells

A biological guide to glycosaminoglycans: current perspectives and pending questions

Neural Tissue Homeostasis and Repair Is Regulated via CS and DS Proteoglycan Motifs

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