The NHERF2 sequence adjacent and upstream of the ERM-binding domain affects NHERF2-ezrin binding and dexamethasone stimulated NHE3 activity

Jianbo Yang, Rafiquel Sarker, Varsha Singh, Prateeti Sarker, Jianyi Yin, Tian E. Chen, Raghothama Chaerkady, Xuhang Li, C. Ming Tse, Mark Donowitz

Research output: Contribution to journalArticle

Abstract

In the brush border of intestinal and kidney epithelial cells, scaffolding proteins ezrin, Na+-H+ exchanger regulatory factor (NHERF)1 and NHERF2 play important roles in linking transmembrane proteins to the cytoskeleton and assembling signalling regulatory complexes. The last 30 carboxyl residues of NHERF1 and NHERF2 form the EBDs [ezrin, radixin and moesin (ERM)-binding domain]. The current study found that NHERF1/2 contain an ERM-binding regulatory sequence (EBRS), which facilitates the interaction between the EBD and ezrin. The EBRSs are located within 24 and 19 residues immediately upstream of EBDs for NHERF1 and NHERF2 respectively. In OK (opossum kidney) epithelial cells, EBRSs are necessary along with the EBD to distribute NHERF1 and NHERF2 exclusively to the apical domain. Furthermore, phosphorylation of Ser303 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 Ser303 was functionally significant preventing acute stimulation of NHE3 (Na+-H+ exchanger 3) activity by dexamethasone.

Original languageEnglish (US)
Pages (from-to)77-90
Number of pages14
JournalBiochemical Journal
Volume470
Issue number1
DOIs
StatePublished - Aug 15 2015

Keywords

  • Epithelial cell
  • Ezrin
  • Microvillus
  • NHE3
  • Na<sup>+</sup>-h<sup>+</sup>exchanger regulatory factor (NHERF)1/2
  • Phosphorylation
  • Radixin and moesin-binding regulatory sequence (EBRS)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'The NHERF2 sequence adjacent and upstream of the ERM-binding domain affects NHERF2-ezrin binding and dexamethasone stimulated NHE3 activity'. Together they form a unique fingerprint.

  • Cite this