GANAB and <i>N</i>-Glycans Substrates Are Relevant in Human Physiology, Polycystic Pathology and Multiple Sclerosis: A Review
Glycans are one of the four fundamental macromolecular components of living matter, and they are highly regulated in the cell. Their functions are metabolic, structural and modulatory. In particular, ER resident <i>N</i>-glycans participate with the Glc<sub>3</sub>Man<sub&...
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| Format: | Article |
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MDPI AG
2022-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/13/7373 |
| _version_ | 1797479622079676416 |
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| author | Roberto De Masi Stefania Orlando |
| author_facet | Roberto De Masi Stefania Orlando |
| author_sort | Roberto De Masi |
| collection | DOAJ |
| description | Glycans are one of the four fundamental macromolecular components of living matter, and they are highly regulated in the cell. Their functions are metabolic, structural and modulatory. In particular, ER resident <i>N</i>-glycans participate with the Glc<sub>3</sub>Man<sub>9</sub>GlcNAc<sub>2</sub> highly conserved sequence, in protein folding process, where the physiological balance between glycosylation/deglycosylation on the innermost glucose residue takes place, according GANAB/UGGT concentration ratio. However, under abnormal conditions, the cell adapts to the glucose availability by adopting an aerobic or anaerobic regimen of glycolysis, or to external stimuli through internal or external recognition patterns, so it responds to pathogenic <i>noxa</i> with unfolded protein response (UPR). UPR can affect Multiple Sclerosis (MS) and several neurological and metabolic diseases via the BiP stress sensor, resulting in ATF6, PERK and IRE1 activation. Furthermore, the abnormal GANAB expression has been observed in MS, systemic lupus erythematous, male germinal epithelium and predisposed highly replicating cells of the kidney tubules and bile ducts. The latter is the case of Polycystic Liver Disease (PCLD) and Polycystic Kidney Disease (PCKD), where genetically induced GANAB loss affects polycystin-1 (PC1) and polycystin-2 (PC2), resulting in altered protein quality control and cyst formation phenomenon. Our topics resume the role of glycans in cell physiology, highlighting the <i>N</i>-glycans one, as a substrate of GANAB, which is an emerging key molecule in MS and other human pathologies. |
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| format | Article |
| id | doaj.art-e3b0c7d8ee594576826933e1585b21d7 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:48:26Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e3b0c7d8ee594576826933e1585b21d72023-11-23T20:12:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012313737310.3390/ijms23137373GANAB and <i>N</i>-Glycans Substrates Are Relevant in Human Physiology, Polycystic Pathology and Multiple Sclerosis: A ReviewRoberto De Masi0Stefania Orlando1Complex Operative Unit of Neurology, “F. Ferrari” Hospital, Casarano, 73042 Lecce, ItalyLaboratory of Neuroproteomics, Multiple Sclerosis Centre, “F. Ferrari” Hospital, Casarano, 73042 Lecce, ItalyGlycans are one of the four fundamental macromolecular components of living matter, and they are highly regulated in the cell. Their functions are metabolic, structural and modulatory. In particular, ER resident <i>N</i>-glycans participate with the Glc<sub>3</sub>Man<sub>9</sub>GlcNAc<sub>2</sub> highly conserved sequence, in protein folding process, where the physiological balance between glycosylation/deglycosylation on the innermost glucose residue takes place, according GANAB/UGGT concentration ratio. However, under abnormal conditions, the cell adapts to the glucose availability by adopting an aerobic or anaerobic regimen of glycolysis, or to external stimuli through internal or external recognition patterns, so it responds to pathogenic <i>noxa</i> with unfolded protein response (UPR). UPR can affect Multiple Sclerosis (MS) and several neurological and metabolic diseases via the BiP stress sensor, resulting in ATF6, PERK and IRE1 activation. Furthermore, the abnormal GANAB expression has been observed in MS, systemic lupus erythematous, male germinal epithelium and predisposed highly replicating cells of the kidney tubules and bile ducts. The latter is the case of Polycystic Liver Disease (PCLD) and Polycystic Kidney Disease (PCKD), where genetically induced GANAB loss affects polycystin-1 (PC1) and polycystin-2 (PC2), resulting in altered protein quality control and cyst formation phenomenon. Our topics resume the role of glycans in cell physiology, highlighting the <i>N</i>-glycans one, as a substrate of GANAB, which is an emerging key molecule in MS and other human pathologies.https://www.mdpi.com/1422-0067/23/13/7373Multiple SclerosisPolycystic Kidney DiseasePolycystic Liver DiseaseER stressGANABPRKCSH |
| spellingShingle | Roberto De Masi Stefania Orlando GANAB and <i>N</i>-Glycans Substrates Are Relevant in Human Physiology, Polycystic Pathology and Multiple Sclerosis: A Review International Journal of Molecular Sciences Multiple Sclerosis Polycystic Kidney Disease Polycystic Liver Disease ER stress GANAB PRKCSH |
| title | GANAB and <i>N</i>-Glycans Substrates Are Relevant in Human Physiology, Polycystic Pathology and Multiple Sclerosis: A Review |
| title_full | GANAB and <i>N</i>-Glycans Substrates Are Relevant in Human Physiology, Polycystic Pathology and Multiple Sclerosis: A Review |
| title_fullStr | GANAB and <i>N</i>-Glycans Substrates Are Relevant in Human Physiology, Polycystic Pathology and Multiple Sclerosis: A Review |
| title_full_unstemmed | GANAB and <i>N</i>-Glycans Substrates Are Relevant in Human Physiology, Polycystic Pathology and Multiple Sclerosis: A Review |
| title_short | GANAB and <i>N</i>-Glycans Substrates Are Relevant in Human Physiology, Polycystic Pathology and Multiple Sclerosis: A Review |
| title_sort | ganab and i n i glycans substrates are relevant in human physiology polycystic pathology and multiple sclerosis a review |
| topic | Multiple Sclerosis Polycystic Kidney Disease Polycystic Liver Disease ER stress GANAB PRKCSH |
| url | https://www.mdpi.com/1422-0067/23/13/7373 |
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