A role of glycerophosphodiesterase EDI3 in glycogen metabolism
| dc.contributor.advisor | Hengstler, Jan Georg | |
| dc.contributor.author | Leonhardt, Gregor M. | |
| dc.contributor.referee | Watzl, Carsten | |
| dc.date.accepted | 2021-02-25 | |
| dc.date.accessioned | 2021-03-25T12:25:47Z | |
| dc.date.available | 2021-03-25T12:25:47Z | |
| dc.date.issued | 2020 | |
| dc.description.abstract | The glycerophosphodiesterase EDI3 (endometrial differential 3) is a key enzyme in various metabolic signalling pathways because it cross-links the triglyceride and choline signalling pathway by hydrolysing glycerophosphocholine (GPC) to glycerol-3-phosphate (G3P) and choline. The enzyme has two functional domains - the GDE domain, where the active site of the protein is located, and the carbohydrate binding domain (CBM), whose function is completely unknown. EDI3 is part of the evolutionary conserved GDE protein family, whose members have different functions. In previous work, high EDI3 expression in primary toumors of ovarian and endometrial carcinomas was associated with increased metastasis, increased cell migration and poorer survival. In this work the role of the CBM20 domain was investigated on a large scale and a possible new role for EDI3 was found. The present work confirms previous research on other CBM20 proteins (Laforin and STBD1) that showed that the CBM domain is essential for protein stability. The deletion of the entire CBM20 domain (ΔCBM20) and mutations of a conserved amino acid within the CBM20 (W32A) significantly reduced protein stability. As a consequence of these mutations, the enzymatic activity of the protein was decreased (W32A) or completely eliminated (ΔCBM20) and the phenotypic migration effect was reduced. Furthermore, this work could show that EDI3 forms dimers or oligomers and the CBM20 domain is required for this process. A characteristic of CBM20 is the interaction with plant starch. For laforin and STBD1, an interaction with glycogen via the CBM20 domain was additionally demonstrated. In this work EDI3 could be associated for the first time with glycogen in vitro and with glycogen-associated proteins of the human skeletal and cardiac muscle. While no binding of EDI3 and glycogen could be detected in human liver, glucagon regulation was observed in primary mouse hepatocytes, potentially linking EDI3 to a role during gluconeogenesis. In skeletal muscle, EDI3 was associated with Type II skeletal muscle cells and the T-tubules, where it co-localizes with ryanodine receptor 1, suggesting a role of EDI3 in calcium signalling. | en |
| dc.identifier.uri | http://hdl.handle.net/2003/40096 | |
| dc.identifier.uri | http://dx.doi.org/10.17877/DE290R-21973 | |
| dc.language.iso | en | de |
| dc.subject | Glycogen | en |
| dc.subject | Muscle | en |
| dc.subject | CBM20 | en |
| dc.subject | EDI3 | en |
| dc.subject | GDE5 | en |
| dc.subject | GYS1 | en |
| dc.subject | STBD1 | en |
| dc.subject.ddc | 540 | |
| dc.subject.ddc | 570 | |
| dc.subject.rswk | Glykogen | de |
| dc.subject.rswk | Enzym | de |
| dc.title | A role of glycerophosphodiesterase EDI3 in glycogen metabolism | en |
| dc.type | Text | de |
| dc.type.publicationtype | doctoralThesis | de |
| dcterms.accessRights | open access | |
| eldorado.secondarypublication | false | de |