Ezrin-radixin-moesin (ERM)-binding phosphoprotein 50 organizes ERM proteins at the apical membrane of polarized epithelia.
Ezrin-radixin-moesin (ERM) proteins regulate the organization and function of specific cortical structures in polarized epithelial cells by connecting filamentous (F)-actin to plasma membrane proteins. The contribution of ERM proteins to these structures depends on a conformational change to an active state in which the C-terminal region interacts with F-actin and the N-terminal domain interacts with membrane ligands. The specific ligands necessary for stabilizing ERM proteins at the membrane are not known. By generating mice deficient for ERM-binding phosphoprotein 50/Na(+)/H(+) exchanger regulatory factor 1 (EBP50/NHERF1), which binds the N-terminal domain of ERM proteins, we found that EBP50 is required for the maintenance of active ERM proteins at the cortical brush border membranes (BBM) of polarized epithelia. In EBP50(-/-) mice, ERM proteins were significantly decreased specifically in BBM from kidney and small intestine epithelial cells, whereas they remained unchanged in the cytoplasm. In wild-type animals, EBP50 was localized to the BBM compartment where it was processed by cleavage of the ERM-binding motif. In BBM, active ERM proteins formed distinct complexes with full-length EBP50 and with F-actin, suggesting a switch mechanism in which proteolytically processed EBP50 would release ERM proteins to complex with F-actin. The structural defects found in the EBP50(-/-) intestinal microvilli were reminiscent of those described in ezrin(-/-) mice, suggesting a role for EBP50 in organizing apical epithelial membranes.
Morales
Fabiana C
FC
Department of Neuro-Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Takahashi
Yoko
Y
Kreimann
Erica L
EL
Georgescu
Maria-Magdalena
MM
D000199:Actins / Q000378:metabolism; D020816:Amino Acid Motifs; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D016764:Cell Polarity; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D017353:Gene Deletion; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology / Q000648:ultrastructure; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D008871:Microvilli / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D046912:Multiprotein Complexes; D010750:Phosphoproteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017923:Sodium-Hydrogen Exchangers; D000099149:Ezrin
D000199:Actins; D001798:Blood Proteins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D046912:Multiprotein Complexes; D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; D000099149:Ezrin; C093376:sodium-hydrogen exchanger regulatory factor; C071058:moesin; C071776:radixin