کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3890033 1249690 2006 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
WNK4 kinase regulates surface expression of the human sodium chloride cotransporter in mammalian cells
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های کلیوی
پیش نمایش صفحه اول مقاله
WNK4 kinase regulates surface expression of the human sodium chloride cotransporter in mammalian cells
چکیده انگلیسی

Pseudohypoaldosteronism type II (PHA II) is caused by mutations of two members of WNK ((with no lysine (k)) kinase family. WNK4 wild type (WT) has been shown to inhibit the activity and surface expression of sodium chloride cotransporter (NCC) when expressed in Xenopus oocytes. Here, we have studied NCC protein processing in mammalian cells in the presence or absence of WNK4 WT and its mutants, E562K and R1185C, by surface biotinylation, Western blot, co-immunoprecipitation (Co-IP) and immunostaining. WNK4 WT significantly reduced NCC surface expression in Cos-7 cells (58.9±6.8% vs 100% in control, P<0.001, n=6), whereas its mutant E562K has no significant effect on NCC surface expression (92.9±5.3% vs 100%, P=NS, n=6). Another mutant R1185C still partially reduces surface expression of NCC (76.2±11.8% vs 100%, P<0.05, n=6). The reduction of NCC surface expression by WNK4 WT (62.9±3.3% of control group) is not altered by WT dynamin ((61.8±3.7% (P=NS)) or its mutant K44A ((65.4±14.1% (P=NS)). A Co-IP study showed that both WNK4 WT and WNK4 E562K interact with NCC. Furthermore, a proton pump inhibitor, bafilomycin A1, partially reverses the inhibitory effect of WNK4 WT on NCC expression. Our data suggest that WNK4 WT significantly inhibits NCC surface expression, which is not owing to an increase in clathrin-mediated endocytosis of NCC, but likely results from enhanced degradation of NCC through a lysosomal pathway.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Kidney International - Volume 69, Issue 12, 2 June 2006, Pages 2162–2170
نویسندگان
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