Published ahead of print on February 2, 2006, doi:10.1165/rcmb.2005-0442OC Am. J. Respir. Cell Mol. Biol., Volume 34, Number 6, June 2006, 754-759 A more recent version of this article appeared on June 1, 2006
Submitted on December 2, 2005 Regulation of the ClC-2 Lung Epithelial Chloride Channel by Glycosylation of SP1Neeraj Vij1 and Pamela L Zeitlin1*1 Department of Pediatrics, Eudowood Division of Pediatric Respiratory Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA * To whom correspondence should be addressed. E-mail: pzeitlin{at}jhmi.edu.
ClC-2 is a pH- and voltage-activated chloride channel that is highly expressed in mammalian fetal airway epithelia during the period of maximal fluid secretion. A high level of luminal ClC-2 protein expression is maintained by the SP1 transcription factor until both SP1 and ClC-2 decline rapidly at birth. Using fetal (preII-19) and adult (L2) rat lung Type 2 cell lines, we demonstrate that the active higher molecular weight 105 kD isoform of SP1 is both phosphorylated and glycosylated. Exposure of either cell line to high dose glutamine is sufficient to induce glycosylation of SP1 and to induce and maintain ClC-2. Exposure to tunicamycin to inhibit SP1 glycosylation reduces ClC-2 expression. We also demonstrate that in vivo ClC-2 expression is similarly regulated. SP1 from six week old murine lung (high ClC-2 expression) is hyperphosphorylated and hyperglycosylated compared to SP1 from 16 week old lung (low ClC-2 expression). Our results support the hypothesis that glycosylation of SP1 produces the 105 kD isoform of SP1 and is involved in regulating ClC-2 gene expression.
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