| pubmed-article:19889841 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:19889841 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
| pubmed-article:19889841 | lifeskim:mentions | umls-concept:C0007634 | lld:lifeskim |
| pubmed-article:19889841 | lifeskim:mentions | umls-concept:C0458827 | lld:lifeskim |
| pubmed-article:19889841 | lifeskim:mentions | umls-concept:C0056889 | lld:lifeskim |
| pubmed-article:19889841 | lifeskim:mentions | umls-concept:C0442805 | lld:lifeskim |
| pubmed-article:19889841 | lifeskim:mentions | umls-concept:C1521761 | lld:lifeskim |
| pubmed-article:19889841 | lifeskim:mentions | umls-concept:C1155964 | lld:lifeskim |
| pubmed-article:19889841 | lifeskim:mentions | umls-concept:C1621574 | lld:lifeskim |
| pubmed-article:19889841 | lifeskim:mentions | umls-concept:C0220905 | lld:lifeskim |
| pubmed-article:19889841 | lifeskim:mentions | umls-concept:C0597484 | lld:lifeskim |
| pubmed-article:19889841 | pubmed:issue | 1 | lld:pubmed |
| pubmed-article:19889841 | pubmed:dateCreated | 2010-1-5 | lld:pubmed |
| pubmed-article:19889841 | pubmed:abstractText | We have demonstrated that Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) overexpression in CFBE41o- cells induces a significant redistribution of F508del cystic fibrosis transmembrane conductance regulator (CFTR) from the cytoplasm to the apical membrane and rescues CFTR-dependent chloride secretion. Here, we observe that CFBE41o- monolayers displayed substantial disassembly of actin filaments and that overexpression of wild-type (wt) NHERF1 but not NHERF1-Delta Ezrin-Radixin-Moesin (ERM) increased F-actin assembly and organization. Furthermore, the dominant-negative band Four-point one, Ezrin, Radixin, Moesin homology (FERM) domain of ezrin reversed the wt NHERF1 overexpression-induced increase in both F-actin and CFTR-dependent chloride secretion. wt NHERF1 overexpression enhanced the interaction between NHERF1 and both CFTR and ezrin and between ezrin and actin and the overexpression of wt NHERF1, but not NHERF1-DeltaERM, also increased the phosphorylation of ezrin in the apical region of the cell monolayers. Furthermore, wt NHERF1 increased RhoA activity and transfection of constitutively active RhoA in CFBE41o- cells was sufficient to redistribute phospho-ezrin to the membrane fraction and rescue both the F-actin content and the CFTR-dependent chloride efflux. Rho kinase (ROCK) inhibition, in contrast, reversed the wt NHERF1 overexpression-induced increase of membrane phospho-ezrin, F-actin content, and CFTR-dependent secretion. We conclude that NHERF1 overexpression in CFBE41o- rescues CFTR-dependent chloride secretion by forming the multiprotein complex RhoA-ROCK-ezrin-actin that, via actin cytoskeleton reorganization, tethers F508del CFTR to the cytoskeleton stabilizing it on the apical membrane. | lld:pubmed |
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| pubmed-article:19889841 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:19889841 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:19889841 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:19889841 | pubmed:month | Jan | lld:pubmed |
| pubmed-article:19889841 | pubmed:issn | 1939-4586 | lld:pubmed |
| pubmed-article:19889841 | pubmed:author | pubmed-author:SeidlerUrsula... | lld:pubmed |
| pubmed-article:19889841 | pubmed:author | pubmed-author:Di... | lld:pubmed |
| pubmed-article:19889841 | pubmed:author | pubmed-author:CasavolaValer... | lld:pubmed |
| pubmed-article:19889841 | pubmed:author | pubmed-author:GuerraLorenzo... | lld:pubmed |
| pubmed-article:19889841 | pubmed:author | pubmed-author:FanelliTeresa... | lld:pubmed |
| pubmed-article:19889841 | pubmed:author | pubmed-author:ConeseMassimo... | lld:pubmed |
| pubmed-article:19889841 | pubmed:author | pubmed-author:CardoneRosa... | lld:pubmed |
