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Publication : CIP1 is an activator of the K+-Cl- cotransporter KCC2.

First Author  Wenz M Year  2009
Journal  Biochem Biophys Res Commun Volume  381
Issue  3 Pages  388-92
PubMed ID  19232517 Mgi Jnum  J:324635
Mgi Id  MGI:7280987 Doi  10.1016/j.bbrc.2009.02.057
Citation  Wenz M, et al. (2009) CIP1 is an activator of the K+-Cl- cotransporter KCC2. Biochem Biophys Res Commun 381(3):388-92
abstractText  In most neurons, efficient setting of the intracellular Cl(-)-concentration requires the coordinated regulation of the Cl(-)-inward transporter NKCC1 and the Cl(-)-outward transporter KCC2. Previously, the cation-chloride cotransporter interacting protein 1 (CIP1) was shown to inactivate NKCC1. Here, we investigated its role for KCC2 activity. After co-expression of CIP1 and KCC2 in HEK-293 cells, a physical and functional interaction was observed. CIP1 co-purified with KCC2 in pull-down experiments and significantly increased KCC2 transport activity, as determined by 86Rb+ flux measurements. RT-PCR analysis demonstrated a ubiquitous expression during postnatal development of the rat. Real-time PCR revealed a two-fold down-regulation of CIP1 during maturation of the rat brain. Taken together, our data identify CIP1 as a potent activator of KCC2. Furthermore, the results support previous data of heteromer formation among members of the cation-chloride cotransporter gene family.
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