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- Title
Characterization of cytoskeletal protein 4.1R interaction with NHE1 (Na<sup>+</sup> /H<sup>+</sup> exchanger isoform 1).
- Authors
NUNOMURA, Wataru; DENKER, Sheryl P.; BARBER, Diane L.; TAKAKUWA, Yuichi; GASCARD, Philippe
- Abstract
NHE1 (Na+ /H+ exchanger isoform 1) has been reported to be hyperactive in 4.1R-null erythrocytes [Rivera, De Franceschi, Peters, Gascard, Mohandas and Brugnara (2006) Am. J. Physiol. Cell Physiol. 291, C880-C886], supporting a functional interaction between NHE1 and 4.1R. In the present paper we demonstrate that 4.1R binds directly to the NHE1cd (cytoplasmic domain of NHE1) through the interaction of an EED motif in the 4.1R FERM (4.1/ezrin/radixin/moesin) domain with two clusters of basic amino acids in the NHE1cd,K519RandR556FNKKYVKK, previously shown to mediate PIP2 (phosphatidylinositol 4,5- bisphosphate) binding [Aharonovitz, Zaun, Balla, York, Orlowski and Grinstein (2000) J. Cell. Biol. 150, 213-224]. The affinity of this interaction (Kd =100-200 nM) is reduced in hypertonic and acidic conditions, demonstrating that this interaction is of an electrostatic nature. The binding affinity is also reduced upon binding of Ca2+ /CaM (Ca2+ -saturated calmodulin) to the 4.1R FERM domain. We propose that 4.1R regulates NHE1 activity through a direct protein-protein interaction that can be modulated by intracellular pH and Na+ and Ca2+ concentrations.
- Publication
Biochemical Journal, 2012, Vol 446, Issue 3, p427
- ISSN
0264-6021
- Publication type
Academic Journal
- DOI
10.1042/BJ20120535