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The NHE3 interacting PDZ protein NHERF2 determines the lipid raft association of the apical Na+/H+ exchanger NHE3 in murine small intestine
Author(s) -
Sultan Ayesha,
Riederer Brigitte,
Xia Weiliang,
Chen Mingmin,
Lamprecht Georg,
Lissner Simone,
Yun Chris,
Jonge Hugo,
Donowitz Mark,
Gessner Johannes,
Seidler Ursula
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1066.3
Subject(s) - lipid raft , raft , pdz domain , microbiology and biotechnology , chemistry , brush border , sodium–hydrogen antiporter , sphingomyelin , membrane , biophysics , biology , biochemistry , vesicle , organic chemistry , sodium , copolymer , polymer
Background Intestinal NHE3 is scaffolded and differentially regulated by Na + /H + Exchanger Regulatory Factor (NHERF) PDZ‐adaptors. NHE3 partially resides in lipid rafts of the Brush Border Membrane (BBM). Aim To investigate if there is a cross talk between NHERFs and membrane rafts, specifically if NHERFs associate differentially with the raft and non‐raft fraction of NHE3, and whether they influence the function and distribution of NHE3 in these microdomains. Methods and Results Murine BBM was detergent‐solubilised and lipid rafts isolated by density gradient floatation. NHE3 was partially, NHERF2 strongly and NHERF1 weakly raft‐associated, and NHERF3 exclusively in the non‐raft fraction. In absence of NHERF2, raft‐associated NHE3 was strongly decreased. Increasing the membrane sphingomyelin/ceramide ratio, increased NHE3‐dependent small intestinal fluid absorption in vivo, as well as overall NHE3 in the lipid rafts, suggesting a positive correlation between NHE3 function and raft association. Conclusions In murine small intestinal BBM, NHE3 differentially associates with the different NHERFs in the raft and non‐raft fraction. NHE3 raft‐association is NHERF2‐dependent. NHE3 and NHERF raft‐association and function are modulated by changes in the lipidic environment. This suggests that PDZ‐scaffolding proteins are involved in the retention of membrane proteins within lipid raft platforms.