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Regulation of SLC26A3 activity by NHERF4 PDZ-mediated interaction.

 Ji Hyun Lee  ;  Joo Hyun Nam  ;  Joonhee Park  ;  Dong-Won Kang  ;  Joo Young Kim  ;  Min Goo Lee  ;  Jae Seok Yoon 
 CELLULAR SIGNALLING, Vol.24(9) : 1821-1830, 2012 
Journal Title
Issue Date
Chloride-Bicarbonate Antiporters/metabolism* ; Epithelial Cells/chemistry ; Epithelial Cells/metabolism ; Gastric Mucosa/chemistry ; Gastric Mucosa/metabolism ; HeLa Cells ; Humans ; PDZ Domains* ; Phosphoproteins/metabolism* ; Sodium-Hydrogen Exchangers/metabolism*
NHERF4 ; SLC26A3 ; PDZ-based protein–protein interactions ; Chloride/bicarbonate exchange ; Phosphorylation
SLC26A3 functions as a chloride/bicarbonate anion exchanger expressed in the secretory epithelial cells in the intestine, pancreas, and salivary glands. SLC26A3 has a C-terminal class I PDZ binding motif that assembles regulatory factors or other transporters by anchoring to various PDZ scaffold proteins. NHERF4 is an epithelial-enriched PDZ domain scaffold protein that has attracted attention because of its enriched tissue expression in the intestine and kidney. In this study, we identified SLC26A3 as a novel binding transporter of NHERF4. We investigated the functional role of NHERF4 in the regulation of SLC26A3 by using integrated biochemical and physiological approaches. A direct protein-protein interaction was identified between the PDZ-binding motif of SLC26A3 and the third PDZ domain of NHERF4. Interaction with NHERF4 decreased the level of SLC26A3 expression on the plasma membrane, which led to reduced SLC26A3 anion exchange activity. Notably, interaction with NHERF4 induced rapid internalisation of SLC26A3 from the plasma membrane. The SLC26A3-NHERF4 interaction was modulated by phosphorylation; serine 329 of NHERF4-PDZ3 played a critical role in modulating binding selectivity. Our findings suggest that NHERF4 is a novel modulator of luminal fluidity in the intestine by adjusting SLC26A3 expression and activity through a phosphorylation-dependent mechanism.
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1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Research Center for Human Natural Defense System (생체방어연구센터) > 1. Journal Papers
Yonsei Authors
Kim, Joo Young(김주영) ORCID logo https://orcid.org/0000-0003-2623-1491
Park, Jun-Hee(박준희)
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
Lee, Ji Hyun(이지현)
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