Ezrin–radixin–moesin (ERM)-binding phosphoprotein 50 organizes ERM proteins at the apical membrane of polarized epithelia
AUTOR(ES)
Morales, Fabiana C.
FONTE
National Academy of Sciences
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=539771Documentos Relacionados
- Nodes of Ranvier form in association with ezrin-radixin-moesin (ERM)-positive Schwann cell processes
- A macromolecular complex of β2 adrenergic receptor, CFTR, and ezrin/radixin/moesin-binding phosphoprotein 50 is regulated by PKA
- Heterotypic and homotypic associations between ezrin and moesin, two putative membrane-cytoskeletal linking proteins.
- Moesin, ezrin, and p205 are actin-binding proteins associated with neutrophil plasma membranes.
- Moesin: a member of the protein 4.1-talin-ezrin family of proteins.