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Localization of proteins for ion transporters, channels and associated enzymes and identification of their corresponding genes in adult and immature rat choroid plexus.

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posted on 2013-07-02, 02:34 authored by Shane A. Liddelow, Katarzyna M. Dziegielewska, C. Joakim Ek, Mark D. Habgood, Hannelore Bauer, Hans-Christian Bauer, Helen Lindsay, Matthew J. Wakefield, Nathalie Strazielle, Ingrid Kratzer, Kjeld Møllgård, Jean-François Ghersi-Egea, Norman R. Saunders

Data for the localisation of the proteins are from a previous study [100] and see also Tables 3 and 4. CSF secretion results from coordinated transport of ions and water from basolateral membrane to cytoplasm, then sequentially across apical membrane into ventricles (for review see [65]). On the plasma-facing membrane is parallel Cl/HCO3 exchange (AE2, Slc4a2) and Na+/HCO3 co-transport (NBC1, Slc4a4) with net function bringing Cl into cells in exchange for HCO3[101]. Also basolaterally located is and Na-dependent Cl/HCO3 exchange (NCBE, Slc4a10) that modulate pH and perhaps CSF formation [102]. Apical Na+ efflux by NHE5 (Slc9a5) and ATB1 (Atb1b1, Na+/K+-ATPase, asterisk) maintains a low cell Na+ that sets up a favorable basolateral gradient to drive Na+ uptake [103]. Na+ is extruded into CSF mainly via the Na+/K+-ATPase pump (ATB1, Atb1b1) and, under some conditions, the Na+/K+/-Cl co-transporter NKCC2, Slc12a2, see [104] for review). Overall cell volume is maintained by the K+/Cl co-transporters NCCT (Slc12a3) and KCC1 (Slc12a4). Aquaporin (AQP1/3/4) channels on CSF-facing membrane mediate water flux into ventricles [105]. Polarized distribution of carbonic anhydrase (CAR) and Na+/K+-ATPase, and aquaporins, enable net ion and water translocation to CSF (see [104], [106] for review). The gene Slc4a7 (NBCn1) was not detected by RNA-Seq, although it has been reported in both rat and mouse choroid plexus [107]); this may have been for technical reasons or because of lack of antibody specificity see section “Limitations of study”. The genes for Clir (chloride inwardly rectifying) channels has not been previously identified but are probably Clica and Clicb. The gene for VRAC (volume regulated anion channels) is not known [108]; see also Table 4. The carbonic anhydrases CAR2 and CAR8 have an intracellular distribution; CAR8 has been shown to lack the characteristic enzyme activity of these proteins [73]. It is not known whether it is functional in the embryo. The CLIC chloride channels are also intracellular [109] and as such we have placed them cytosolically, however it is more likely that they sit on the internal membrane of the cell and aid in movement of Cl to other channels. The inset boxes show the fold differences for genes expressed at a higher level in the embryonic (red) or in the adult (green) choroid plexus.

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