Absence of EPAC1 Signaling to Stabilize CFTR in Intestinal Organoids

被引:2
|
作者
Ferreira, Joao F. [1 ]
Silva, Iris A. L. [1 ]
Botelho, Hugo M. [1 ]
Amaral, Margarida D. [1 ]
Farinha, Carlos M. [1 ]
机构
[1] Univ Lisbon, Fac Sci, BioISI Biosyst & Integrat Sci Inst, P-1749016 Lisbon, Portugal
关键词
CFTR; Cystic Fibrosis; cAMP signaling; EPAC1; membrane stability; intestinal organoids; CYSTIC-FIBROSIS; ENDOPLASMIC-RETICULUM; ACTIN CYTOSKELETON; CAMP; MEMBRANE; MECHANISM; ENDOCYTOSIS; ACTIVATION; FAMILY;
D O I
10.3390/cells11152295
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The plasma membrane (PM) stability of the cystic fibrosis transmembrane conductance regulator (CFTR), the protein which when mutated causes Cystic Fibrosis (CF), relies on multiple interaction partners that connect CFTR to signaling pathways, including cAMP signaling. It was previously shown that activation of exchange protein directly activated by cAMP 1 (EPAC1) by cAMP promotes an increase in CFTR PM levels in airway epithelial cells. However, the relevance of this pathway in other tissues, particularly the intestinal tissue, remains uncharacterized. Here, we used Western blot and forskolin-induced swelling assay to demonstrate that the EPAC1 protein is not expressed in the intestinal organoid model, and consequently the EPAC1 stabilization pathway is not in place. On the other hand, using cell surface biotinylation, EPAC1-mediated stabilization of PM CFTR is observed in intestinal cell lines. These results indicate that the EPAC1 stabilization pathway also occurs in intestinal cells and is a potential target for the development of novel combinatorial therapies for treatment of CF.
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页数:11
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