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PMID:20215404

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Citation

Hughes, SC, Formstecher, E and Fehon, RG (2010) Sip1, the Drosophila orthologue of EBP50/NHERF1, functions with the sterile 20 family kinase Slik to regulate Moesin activity. J. Cell. Sci. 123:1099-107

Abstract

Organization of the plasma membrane in polarized epithelial cells is accomplished by the specific localization of transmembrane or membrane-associated proteins, which are often linked to cytoplasmic protein complexes, including the actin cytoskeleton. In this study, we identified Sip1 as a Drosophila orthologue of the ezrin-radixin-moesin (ERM) binding protein 50 (EBP50; also known as the Na(+)/H(+) exchanger regulatory factor NHERF1). In mammals, EBP50/NHERF1 is a scaffold protein required for the regulation of several transmembrane receptors and downstream signal transduction activity. In Drosophila, loss of Sip1 leads to a reduction in Slik kinase protein abundance, loss of Moesin phosphorylation and changes in epithelial structure, including mislocalization of E-cadherin and F-actin. Consistent with these findings, Moesin and Sip1 act synergistically in genetic-interaction experiments, and Sip1 protein abundance is dependent on Moesin. Co-immunoprecipitation experiments indicate that Sip1 forms a complex with both Moesin and Slik. Taken together, these data suggest that Sip1 promotes Slik-dependent phosphorylation of Moesin, and suggests a mechanism for the regulation of Moesin activity within the cell to maintain epithelial integrity.

Links

PubMed PMC2844318 Online version:10.1242/jcs.059469

Keywords

Actins/metabolism; Animals; Cadherins/metabolism; Cell Membrane/metabolism; Cell Polarity; Drosophila; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Epithelial Cells/metabolism; Epithelial Cells/pathology; GTP Phosphohydrolases/genetics; GTP Phosphohydrolases/metabolism; Humans; Membrane Proteins/metabolism; Phosphoproteins/genetics; Protein Binding; Protein Transport; Protein-Serine-Threonine Kinases/metabolism; Septins; Signal Transduction; Sodium-Hydrogen Antiporter/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:Q7K5M6

involved_in

GO:0030036: actin cytoskeleton organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q7K5M6

is_active_in

GO:0098592: cytoplasmic side of apical plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:Q7K5M6

involved_in

GO:0010669: epithelial structure maintenance

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0011661

P

Seeded From UniProt

complete

DROME:Q7K5M6

enables

GO:0060090: molecular adaptor activity

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0011661,FB:FBgn0035001

F

Seeded From UniProt

complete


See also

References

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