Abstract:
:Proper control of NaCl excretion in the kidney is central to bodily functions, yet many mechanisms that regulate reabsorption of sodium and chloride in the kidney remain incompletely understood. Here, we identify an important role played by the intracellular sorting receptor SORLA (sorting protein-related receptor with A-type repeats) in functional activation of renal ion transporters. We demonstrate that SORLA is expressed in epithelial cells of the thick ascending limb (TAL) of Henle's loop and that lack of receptor expression in this cell type in SORLA-deficient mice results in an inability to properly reabsorb sodium and chloride during osmotic stress. The underlying cellular defect was correlated with an inability of the TAL to phosphorylate Na(+)-K(+)-Cl(-) cotransporter 2 (NKCC2), the major sodium transporter in the distal nephron. SORLA functionally interacts with Ste-20-related proline-alanine-rich kinase (SPAK), an activator of NKCC2, and receptor deficiency is associated with missorting of SPAK. Our data suggest a novel regulatory pathway whereby intracellular trafficking of SPAK by the sorting receptor SORLA is crucial for proper NKCC2 activation and for maintenance of renal ion balance.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Reiche J,Theilig F,Rafiqi FH,Carlo AS,Militz D,Mutig K,Todiras M,Christensen EI,Ellison DH,Bader M,Nykjaer A,Bachmann S,Alessi D,Willnow TEdoi
10.1128/MCB.01560-09subject
Has Abstractpub_date
2010-06-01 00:00:00pages
3027-37issue
12eissn
0270-7306issn
1098-5549pii
MCB.01560-09journal_volume
30pub_type
杂志文章abstract::The phorbol ester receptor protein kinase C (PKC) gene family encodes essential mediators of eukaryotic cellular signals. Molecular dissection of their mechanisms of action has been limited in part by the lack of random mutagenesis approaches and by the complexity of signaling pathways in mammalian cells which involve...
journal_title:Molecular and cellular biology
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.4.1079-1093.2002
更新日期:2002-02-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2007-12-01 00:00:00
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