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.
引用
收藏
页数:11
相关论文
共 50 条
  • [1] Microvascular permeability in the absence of Epac1 activity
    Karlsen, Tine Veronica
    Kopperud, Reidun
    Liden, Asa
    Rygh, Cecilie Brekke
    Reed, Rolf K.
    Doskeland, Stein Ove
    FASEB JOURNAL, 2012, 26
  • [2] Characterization of membrane complexes involved in CFTR stabilization by EPAC1 activation
    Santos, J. D.
    Pinto, F. R.
    Amaral, M. D.
    Zaccolo, M.
    Farinha, C. M.
    FEBS OPEN BIO, 2018, 8 : 393 - 393
  • [3] Membranes prime the RapGEF EPAC1 to transduce cAMP signaling
    Sartre, Candice
    Peurois, Francois
    Ley, Marie
    Kryszke, Marie-Helene
    Zhang, Wenhua
    Courilleau, Delphine
    Fischmeister, Rodolphe
    Ambroise, Yves
    Zeghouf, Mahel
    Cianferani, Sarah
    Ferrandez, Yann
    Cherfils, Jacqueline
    NATURE COMMUNICATIONS, 2023, 14 (01)
  • [4] Membranes prime the RapGEF EPAC1 to transduce cAMP signaling
    Candice Sartre
    François Peurois
    Marie Ley
    Marie-Hélène Kryszke
    Wenhua Zhang
    Delphine Courilleau
    Rodolphe Fischmeister
    Yves Ambroise
    Mahel Zeghouf
    Sarah Cianferani
    Yann Ferrandez
    Jacqueline Cherfils
    Nature Communications, 14
  • [5] EPAC1 activation by cAMP stabilizes CFTR at the membrane by promoting its interaction with NHERF1
    Lobo, Miguel J.
    Amaral, Margarida D.
    Zaccolo, Manuela
    Farinha, Carlos M.
    JOURNAL OF CELL SCIENCE, 2016, 129 (13) : 2599 - 2612
  • [6] Distinct roles of Epac1 and Epac2 in M3 muscarinic receptor signaling
    de Jesus, M. Lopez
    Grandoch, M.
    Mahlke, Y.
    Weernink, P. A. Oude
    Jakobs, K. H.
    Schmidt, M.
    NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2007, 375 (02) : 150 - 151
  • [7] Involvement of cAMP Signaling Mediators, Epac1, Epac2 and Rap1 in Decidualization of Rat Uterus
    Yoshie, Mikihiro
    Kusama, Kazuya
    Tamura, Kazuhiro
    Daikoku, Takiko
    Takarada, Tsutomu
    Tachikawa, Eiichi
    ENDOCRINE REVIEWS, 2014, 35 (03)
  • [8] CYTOSKELETON REGULATORS ASSOCIATE WITH CFTR TO CONTROL ITS MEMBRANE LEVELS UNDER EPAC1 ACTIVATION
    Santos, J. D.
    Amaral, M. D.
    Pinto, F. R.
    Farinha, C. M.
    PEDIATRIC PULMONOLOGY, 2019, 54 : S198 - S198
  • [9] EPAC1 Boosts Macrophage Appetite: Implication of EPAC1 in Foam Cell Formation during Atherosclerosis
    Robichaux, William Gene
    Mei, Fang C.
    Sun, Hua
    Wang, Hui
    Yang, Wenli
    Teng, Ba-Bie
    Cheng, Xiaodong
    FASEB JOURNAL, 2018, 32 (01):
  • [10] Role of EPAC1 in chronic pain
    Jiang, Chenlu
    Zhao, Jiacheng
    Zhang, Yihang
    Zhu, Xiang
    BIOCHEMISTRY AND BIOPHYSICS REPORTS, 2024, 37