The NHERF2 sequence adjacent and upstream of the ERM-binding domain affects NHERF2-ezrin binding and dexamethasone stimulated NHE3 activity.
Bottom Line: The current study found that NHERF1/2 contain an ERM-binding regulatory sequence (EBRS), which facilitates the interaction between the EBD and ezrin.Furthermore, phosphorylation of Ser(303) located in the EBRS of NHERF2, decreases the binding affinity for ezrin, dislocates apical NHERF2 into the cytosol and increases the NHERF2 microvillar mobility rate.Moreover, increased phosphorylation of Ser(303) was functionally significant preventing acute stimulation of NHE3 (Na(+)-H(+) exchanger 3) activity by dexamethasone.
Affiliation: Departments of Medicine, Division of Gastroenterology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, U.S.A.Show MeSH
Mentions: The functional significance of phosphorylation of NHERF2–Ser303 was examined by exposing OK cells to dexamethasone for 4 h. Dexamethasone is known to stimulate NHE3 by an acute NHERF2-dependent effect that does not involve stimulation of transcription of NHE3 . OK cells do not express detectable endogenous NHERF2 . As shown in Figure 11, dexamethasone exposure stimulated NHE3 similarly in the presence of exogenous WT NHERF2 and NHERF2–S303A but not when NHERF2–S303D was expressed. NHE3–S303D basal activity was increased compared with WT NHE3 (Figure 11). These results are consistent with the dexamethasone effect requiring NHERF2–ezrin binding to mediate the assembly of a NHE3 signalling complex on the apical membrane  and demonstrate functional significance of phosphorylation of NHERF2–Ser303.
Affiliation: Departments of Medicine, Division of Gastroenterology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, U.S.A.