CIP1 is an activator of the K+-Cl- cotransporter KCC2.
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.
Wenz
Meike
M
Animal Physiology Group, Department of Biology, University of Kaiserslautern, Erwin-Schrödinger-Strasse 13, D-67633 Kaiserslautern, Germany.
Hartmann
Anna-Maria
AM
Friauf
Eckhard
E
Nothwang
Hans Gerd
HG
D000818:Animals; D002460:Cell Line; D006801:Humans; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics / Q000378:metabolism*; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D000096922:K Cl- Cotransporters
D028021:Sodium-Potassium-Chloride Symporters; D027981:Symporters; D000096922:K Cl- Cotransporters