Genetic ablation of Slc4a10 alters the expression pattern of transporters involved in solute movement in the mouse choroid plexus
- PMID: 22357733
- DOI: 10.1152/ajpcell.00285.2011
Genetic ablation of Slc4a10 alters the expression pattern of transporters involved in solute movement in the mouse choroid plexus
Abstract
Mutational changes of one transporter can have deleterious effects on epithelial function leaving the cells with the options of either compensating for the loss of function or dedifferentiating. Previous studies have shown that the choroid plexus epithelium (CPE) from mice lacking the Na(+)-dependent Cl(-)/HCO(3)(-) exchanger (NCBE) encoded by Slc4a10 leads to retargeting of the Na(+)/H(+) exchanger 1 (NHE1) from the luminal to the basolateral plasma membrane. We hypothesized that disruption of NCBE, the main basolateral Na(+) importer in the CPE, would lead to a compensatory increase in the abundance of other important transport proteins in this tissue. Aquaporin-1 (AQP1) abundance was 42.7% lower and Na,K-ATPase 36.4% lower in the CPE of Slc4a10 knockout mice, respectively. The NHE1 binding ezrin cytoskeleton appeared disrupted in Slc4a10 knockout mice, whereas no changes were observed in cellular polarization with respect to claudin-2 and appearance of luminal surface microvilli. The renal proximal tubule constitutes a leaky epithelium with high transport rate similar to CPE. Here, Slc4a10 knockout did not affect Na,K-ATPase or AQP1 expression. CPE from AQP1 knockout mice has a secretory defect similar to Slc4a10 mice. However, neither NCBE nor Na,K-ATPase expression was affected in CPE from AQP1 knockout mice. By contrast, the abundance of Na,K-ATPase and NBCe1 was decreased by 23 and 31.7%, respectively, in AQP1 knockout proximal tubules, while the NHE3 abundance was unchanged. In conclusion, CPE lacking NCBE seems to spare the molecular machinery involved in CSF secretion rather than compensate for the loss of the Na(+) loader. Slc4a10 knockout seems to be more deleterious to CPE than AQP1 knockout.
Similar articles
-
Nhe1 is a luminal Na+/H+ exchanger in mouse choroid plexus and is targeted to the basolateral membrane in Ncbe/Nbcn2-null mice.Am J Physiol Cell Physiol. 2009 Jun;296(6):C1291-300. doi: 10.1152/ajpcell.00062.2009. Epub 2009 Apr 15. Am J Physiol Cell Physiol. 2009. PMID: 19369449 Free PMC article.
-
Distribution of sodium transporters and aquaporin-1 in the human choroid plexus.Am J Physiol Cell Physiol. 2006 Jul;291(1):C59-67. doi: 10.1152/ajpcell.00433.2005. Epub 2006 Feb 15. Am J Physiol Cell Physiol. 2006. PMID: 16481371
-
Polarization of membrane associated proteins in the choroid plexus epithelium from normal and slc4a10 knockout mice.Front Physiol. 2013 Nov 27;4:344. doi: 10.3389/fphys.2013.00344. eCollection 2013. Front Physiol. 2013. PMID: 24348423 Free PMC article.
-
Na(+) dependent acid-base transporters in the choroid plexus; insights from slc4 and slc9 gene deletion studies.Front Physiol. 2013 Oct 22;4:304. doi: 10.3389/fphys.2013.00304. Front Physiol. 2013. PMID: 24155723 Free PMC article. Review.
-
Mechanisms of CSF secretion by the choroid plexus.Microsc Res Tech. 2001 Jan 1;52(1):49-59. doi: 10.1002/1097-0029(20010101)52:1<49::AID-JEMT7>3.0.CO;2-C. Microsc Res Tech. 2001. PMID: 11135448 Review.
Cited by 14 articles
-
Genetic disruption of slc4a10 alters the capacity for cellular metabolism and vectorial ion transport in the choroid plexus epithelium.Fluids Barriers CNS. 2020 Jan 7;17(1):2. doi: 10.1186/s12987-019-0162-5. Fluids Barriers CNS. 2020. PMID: 31906971 Free PMC article.
-
Physiological and pathological impact of AQP1 knockout in mice.Biosci Rep. 2019 May 14;39(5):BSR20182303. doi: 10.1042/BSR20182303. Print 2019 May 31. Biosci Rep. 2019. PMID: 31023968 Free PMC article. Review.
-
Targeting Germinal Matrix Hemorrhage-Induced Overexpression of Sodium-Coupled Bicarbonate Exchanger Reduces Posthemorrhagic Hydrocephalus Formation in Neonatal Rats.J Am Heart Assoc. 2018 Jan 31;7(3):e007192. doi: 10.1161/JAHA.117.007192. J Am Heart Assoc. 2018. PMID: 29386206 Free PMC article.
-
Mouse models of SLC4-linked disorders of HCO3--transporter dysfunction.Am J Physiol Cell Physiol. 2018 May 1;314(5):C569-C588. doi: 10.1152/ajpcell.00301.2017. Epub 2018 Jan 31. Am J Physiol Cell Physiol. 2018. PMID: 29384695 Free PMC article. Review.
-
Liver X receptors regulate cerebrospinal fluid production.Mol Psychiatry. 2016 Jun;21(6):844-56. doi: 10.1038/mp.2015.133. Epub 2015 Sep 1. Mol Psychiatry. 2016. PMID: 26324101
Publication types
MeSH terms
Substances
LinkOut - more resources
-
Full Text Sources
-
Other Literature Sources
-
Molecular Biology Databases
-
Research Materials
-
Miscellaneous