Direct binding of the Na--H exchanger NHE1 to ERM proteins regulates the cortical cytoskeleton and cell shape independently of H(+) translocation.
The association of actin filaments with the plasma membrane maintains cell shape and adhesion. Here, we show that the plasma membrane ion exchanger NHE1 acts as an anchor for actin filaments to control the integrity of the cortical cytoskeleton. This occurs through a previously unrecognized structural link between NHE1 and the actin binding proteins ezrin, radixin, and moesin (ERM). NHE1 and ERM proteins associate directly and colocalize in lamellipodia. Fibroblasts expressing NHE1 with mutations that disrupt ERM binding, but not ion translocation, have impaired organization of focal adhesions and actin stress fibers, and an irregular cell shape. We propose a structural role for NHE1 in regulating the cortical cytoskeleton that is independent of its function as an ion exchanger.
Denker
S P
SP
Department of Stomatology, University of California, San Francisco, San Francisco, CA 94143, USA.
Huang
D C
DC
Orlowski
J
J
Furthmayr
H
H
Barber
D L
DL
D000595:Amino Acid Sequence; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D048429:Cell Size; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D006859:Hydrogen / Q000378:metabolism*; D017136:Ion Transport; D008565:Membrane Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009154:Mutation; D010750:Phosphoproteins / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D011522:Protons; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017923:Sodium-Hydrogen Exchangers / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D022502:Stress Fibers / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D000099149:Ezrin
D001798:Blood Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D006859:Hydrogen; D008565:Membrane Proteins; D010750:Phosphoproteins; D011522:Protons; D011993:Recombinant Fusion Proteins; D017923:Sodium-Hydrogen Exchangers; D014157:Transcription Factors; D000099149:Ezrin; C086680:ETV5 protein, human; C069139:growth factor-activatable Na-H exchanger NHE-1; C071776:radixin