RGD Reference Report - NHE3 regulatory factor 1 (NHERF1) modulates intestinal sodium-dependent phosphate transporter (NaPi-2b) expression in apical microvilli. - Rat Genome Database

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NHE3 regulatory factor 1 (NHERF1) modulates intestinal sodium-dependent phosphate transporter (NaPi-2b) expression in apical microvilli.

Authors: Giral, H  Cranston, D  Lanzano, L  Caldas, Y  Sutherland, E  Rachelson, J  Dobrinskikh, E  Weinman, EJ  Doctor, RB  Gratton, E  Levi, M 
Citation: Giral H, etal., J Biol Chem. 2012 Oct 12;287(42):35047-56. doi: 10.1074/jbc.M112.392415. Epub 2012 Aug 17.
RGD ID: 7207458
Pubmed: PMID:22904329   (View Abstract at PubMed)
PMCID: PMC3471691   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M112.392415   (Journal Full-text)

P(i) uptake in the small intestine occurs predominantly through the NaPi-2b (SLC34a2) co-transporter. NaPi-2b is regulated by changes in dietary P(i) but the mechanisms underlying this regulation are largely undetermined. Sequence analyses show NaPi-2b has a PDZ binding motif at its C terminus. Immunofluorescence imaging shows NaPi-2b and two PDZ domain containing proteins, NHERF1 and PDZK1, are expressed in the apical microvillar domain of rat small intestine enterocytes. Co-immunoprecipitation studies in rat enterocytes show that NHERF1 associates with NaPi-2b but not PDZK1. In HEK co-expression studies, GFP-NaPi-2b co-precipitates with FLAG-NHERF1. This interaction is markedly diminished when the C-terminal four amino acids are truncated from NaPi-2b. FLIM-FRET analyses using tagged proteins in CACO-2(BBE) cells show a distinct phasor shift between NaPi-2b and NHERF1 but not between NaPi-2b and the PDZK1 pair. This shift demonstrates that NaPi-2b and NHERF1 reside within 10 nm of each other. NHERF1(-/-) mice, but not PDZK1(-/-) mice, had a diminished adaptation of NaPi-2b expression in response to a low P(i) diet. Together these studies demonstrate that NHERF1 associates with NaPi-2b in enterocytes and regulates NaPi-2b adaptation.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
apical plasma membrane  IDA 7207458; 7207458; 7207458 RGD 
microvillus membrane  IDA 7207458; 7207458; 7207458 RGD 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Nherf1  (NHERF family PDZ scaffold protein 1)
Pdzk1  (PDZ domain containing 1)
Slc34a2  (solute carrier family 34 member 2)


Additional Information