PubMed 16456185

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: ClvC2 , ClvC4 , Kir6.2

Title: Regulation of the ClC-2 lung epithelial chloride channel by glycosylation of SP1.

Authors: Neeraj Vij, Pamela L Zeitlin

Journal, date & volume: Am. J. Respir. Cell Mol. Biol., 2006 Jun , 34, 754-9

PubMed link:

Chloride channel-2 (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 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 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 6-wk-old murine lung (high ClC-2 expression) is hyperphosphorylated and hyperglycosylated compared with SP1 from 16-wk-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.