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(Received for publication, April 3, 1996)
From the Departments of Human Physiology and
§ Biological Chemistry, University of California School of
Medicine, Davis, California 95616
Using a combination of data base searching,
polymerase chain reaction, and library screening, we have identified a
putative K-Cl cotransporter isoform (KCC2) in rat brain that is
specifically localized in neurons. A cDNA of 5566 bases was
obtained from overlapping clones and encoded a protein of 1116 amino
acids with a deduced molecular mass of 123.6 kDa. Over its full length,
the amino acid sequence of KCC2 is 67% identical to the widely
distributed K-Cl cotransporter isoform (KCC1) identified in rat brain
and rabbit kidney (Gillen, C., Brill, S., Payne, J.A., and Forbush, B.,
III (1996) J. Biol. Chem. 271, 16237-16244) but only
~25% identical to other members of the cation-chloride cotransporter
gene family, including ``loop'' diuretic-sensitive Na-K-Cl
cotransport and thiazide-sensitive Na-Cl cotransport. Based on analysis
of the primary structure as well as homology with other cation-chloride
cotransporters, we predict 12 transmembrane segments bounded by N- and
C-terminal cytoplasmic regions. Four sites for N-linked
glycosylation are predicted on an extracellular intermembrane loop
between putative transmembrane segments 5 and 6. Northern blot analysis
using a KCC2-specific cDNA probe revealed a very highly expressed
~5.6-kilobase transcript only in brain. Reverse
transcriptase-polymerase chain reaction revealed that KCC1 was present
in rat primary astrocytes and rat C6 glioma cells but that KCC2 was
completely absent from these cells, suggesting KCC2 was not of glial
cell origin. In situ hybridization studies demonstrated
that the KCC2 transcript was expressed at high levels in neurons
throughout the central nervous system, including CA1-CA4 pyramidal
neurons of the hippocampus, granular cells and Purkinje neurons of the
cerebellum, and many groups of neurons throughout the brainstem.
Volume 271, Number 27,
Issue of July 5, 1996
pp. 16245-16252
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
A NEURONAL-SPECIFIC ISOFORM
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