Genetic disruption of slc4a10 alters the capacity for cellular metabolism and vectorial ion transport in the choroid plexus epithelium
| Autor: | Jeppe Praetorius, Marianne Skals, Christian A. Hübner, Inga Baasch Christensen, Helle Hasager Damkier, Robert A. Fenton, Anders Solitander Bohlbro, Qi Wu |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Choroid plexus lcsh:RC346-429 Epithelium 03 medical and health sciences Cellular and Molecular Neuroscience Cerebrospinal fluid secretion 0302 clinical medicine Cerebrospinal fluid Developmental Neuroscience Choroid Plexus Epithelium Ncbe Animals Chloride-Bicarbonate Antiporters Ion transporter lcsh:Neurology. Diseases of the nervous system Mice Knockout Water transport Ion Transport Mass spectrometry Chemistry Research Sodium-Bicarbonate Symporters Biological Transport Epithelial Cells General Medicine Metabolism Hydrogen-Ion Concentration Cell biology Transport protein 030104 developmental biology Neurology sense organs 030217 neurology & neurosurgery |
| Zdroj: | Fluids and Barriers of the CNS Christensen, I B, Wu, Q, Bohlbro, A S, Skals, M G, Damkier, H H, Hübner, C A, Fenton, R A & Praetorius, J 2020, ' Genetic disruption of slc4a10 alters the capacity for cellular metabolism and vectorial ion transport in the choroid plexus epithelium ', Fluids and Barriers of the CNS, vol. 17, no. 1, 2 . https://doi.org/10.1186/s12987-019-0162-5 Fluids and Barriers of the CNS, Vol 17, Iss 1, Pp 1-18 (2020) |
| ISSN: | 2045-8118 |
| Popis: | BackgroundGenetic disruption ofslc4a10, which encodes the sodium-dependent chloride/bicarbonate exchanger Ncbe, leads to a major decrease in Na+-dependent HCO3−import into choroid plexus epithelial cells in mice and to a marked reduction in brain intraventricular fluid volume. This suggests that Ncbe functionally is a key element in vectorial Na+transport and thereby for cerebrospinal fluid secretion in the choroid plexus. However,slc4a10disruption results in severe changes in expression of Na+,K+-ATPase complexes and other major transport proteins, indicating that profound cellular changes accompany the genetic manipulation.MethodsA tandem mass tag labeling strategy was chosen for quantitative mass spectrometry. Alterations in the broader patterns of protein expression in the choroid plexus in response to genetic disruption of Ncbe was validated by semi-quantitative immunoblotting, immunohistochemistry and morphometry.ResultsThe abundance of 601 proteins were found significantly altered in the choroid plexus from Ncbe ko mice relative to Ncbe wt. In addition to a variety of transport proteins, particularly large changes in the abundance of proteins involved in cellular energy metabolism were detected in the Ncbe ko mice. In general, the abundance of rate limiting glycolytic enzymes and several mitochondrial enzymes were reduced followingslc4a10disruption. Surprisingly, this was accompanied by increased ATP levels in choroid plexus cells, indicating that the reduction in capacity for energy metabolism was adaptive to high ATP rather than causal for a decreased capacity for ion and water transport. Ncbe-deficient cells also had a reduced cell area and decreased K+content.ConclusionOur findings suggest that the lack of effective Na+-entry into the epithelial cells of the choroid plexus leads to a profound change in the cellular phenotype, shifting from a high-rate secretory function towards a more dormant state; similar to what is observed during ageing or Alzheimer’s disease. |
| Databáze: | OpenAIRE |
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