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The human embryonic-fetal kidney endoplasmic reticulum phosphate-pyrophosphate transport protein
R Hume1, H Brewerton, A Burchell
1Department of Obstetrics and Gynaecology, University of Dundee, UK.
Insights
Glucose-6-phosphatase transporter T2beta develops in human kidneys, mirroring the enzyme
Area of Science:
- Biochemistry
- Developmental Biology
- Molecular Genetics
Background:
- Glucose-6-phosphatase (G6Pase) is a key enzyme system in glucose homeostasis, localized in the endoplasmic reticulum.
- The G6Pase system involves multiple proteins, including transport proteins like T2beta, crucial for substrate and product transport.
- Deficiency in T2beta leads to glycogen storage disease type 1c, highlighting its importance in metabolic pathways.
Purpose of the Study:
- To investigate the temporal and spatial development of the T2beta transporter in human embryonic and fetal kidney.
- To correlate T2beta expression patterns with the glucose-6-phosphatase enzyme during kidney ontogeny.
- To assess the functional capacity of pyrophosphate transport in developing human kidney compared to liver.
Main Methods:
- Immunohistochemistry using anti-T2beta antibodies on human embryonic and fetal kidney tissues.
- Image analysis to quantify and map T2beta expression patterns.
- Kinetic analysis of the glucose-6-phosphatase system and pyrophosphate transport.
Main Results:
- T2beta expression in metanephric kidney initially predominates in ureteric bud derivatives.
- Expression shifts to developing nephrons, particularly proximal tubules, by mid-gestation.
- T2beta exhibits similar spatial and temporal patterns to the G6Pase enzyme in both mesonephric and metanephric kidneys; pyrophosphate transport capacity aligns with G6Pase activity in fetal kidney, unlike in the liver.
Conclusions:
- The developmental pattern of T2beta in the human kidney is closely linked to that of the G6Pase enzyme.
- Functional pyrophosphate transport develops appropriately in the fetal kidney, supporting G6Pase activity.
- Understanding G6Pase protein expression is vital for elucidating the etiology of renal diseases and glycogen storage diseases.
Abstract:
Glucose-6-phosphatase is a multicomponent endoplasmic reticulum system comprising at least six different proteins, including a lumenal enzyme and several transport proteins. One of the transport proteins, T2beta, transports the substrate pyrophosphate and the product phosphate and its genetic deficiency is termed type 1c glycogen storage disease. We have used anti-T2beta antibodies for immunohistochemistry with image analysis and kinetic analysis of the glucose-6-phosphatase system to study for the temporal and spatial development of T2beta in human embryonic and fetal kidney. In metanephric kidney, there is an early predominance of T2beta expression in the ureteric bud derivatives and this changes with ontogeny such that developing nephrons, particularly proximal tubules, become dominant by mid-gestation. T2beta has the same spatial and temporal pattern as the glucose-6-phosphatase enzyme in both mesonephric and metanephric kidney. Pyrophosphate transport capacity is appropriate for the amount of glucose-6-phosphatase activity present in mid-gestation fetal kidney, in contrast to liver, where pyrophosphate transport capacity is developmentally delayed. Increasing knowledge of the temporal and spatial expression of the glucose-6-phosphatase proteins and their catalytic roles in early human development is essential for the elucidation of the aetiology of renal disease in both type I glycogen storage diseases and the developmental disorders of the glucose-6-phosphatase system.