Targeting of CFTR protein is linked to the polarization of human pancreatic duct cells in culture

Hollande, E; Fanjul, Marjorie; Chemin-Thomas, C; Devaux, Christiane; Demolombe, Sophie; Rietschoten, Jurphas Van; Guy-Crotte, Odette; Figarella, Catherine

doi:10.1016/s0171-9335(98)80037-x

Cited by 22 publications

(17 citation statements)

References 30 publications

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“…The dependence of ∆F508 CFTR maturation and targeting upon epithelial polarization has recently been demonstrated in stably transfected cells, as well as in endogenous CFTR-expressing epithelial cells (51,52).…”

Section: Discussionmentioning

confidence: 97%

ΔF508 CFTR protein expression in tissues from patients with cystic fibrosis

Kälin¹,

Claass²,

Sommer³

et al. 1999

J. Clin. Invest.

250

179

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Section: Discussionmentioning

confidence: 97%

ΔF508 CFTR protein expression in tissues from patients with cystic fibrosis

Kälin¹,

Claass²,

Sommer³

et al. 1999

J. Clin. Invest.

250

179

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“…Our observation that CFTR is present in tracheal tight junctions sheds new light on the regulation of tight junctions by CFTR, and future studies will be required to determine whether these regulatory processes are involved in the CFTR-dependent modulation of the ZO-1-ZONAB pathway in the respiratory tract. Interestingly, a potential link between CFTR and epithelial cell polarization has previously been proposed (Hollande et al, 1998) but the underlying mechanism remained unclear. In addition, increased proliferative activity was observed in intestinal crypt epithelial cells of CFTR-null mice (Gallagher and Gottlieb, 2001).…”

Section: Discussionmentioning

confidence: 99%

CFTR interacts with ZO-1 to regulate tight junction assembly and epithelial differentiation via the ZONAB pathway

Ruan

Wang

Silva

et al. 2014

Journal of Cell Science

102

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Mutations in CFTR lead to dysfunction of tubular organs, which is currently attributed to impairment of its conductive properties. We now show that CFTR regulates tight junction assembly and epithelial cell differentiation through modulation of the ZO-1-ZONAB pathway. CFTR colocalizes with ZO-1 at the tight junctions of trachea and epididymis, and is expressed before ZO-1 in Wolffian ducts. CFTR interacts with ZO-1 through the CTFR PDZ-binding domain. In a three-dimensional (3D) epithelial cell culture model, CFTR regulates tight junction assembly and is required for tubulogenesis. CFTR inhibition or knockdown reduces ZO-1 expression and induces the translocation of the transcription factor ZONAB (also known as YBX3) from tight junctions to the nucleus, followed by upregulation of the transcription of CCND1 and downregulation of ErbB2 transcription. The epididymal tubules of cftr 2/2 and cftr DF508 mice have reduced ZO-1 levels, increased ZONAB nuclear expression, and decreased epithelial cell differentiation, illustrated by the reduced expression of apical AQP9 and V-ATPase. This study provides a new paradigm for the etiology of diseases associated with CFTR mutations, including cystic fibrosis.

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“…Immunolocalizations of CFTR were carried out in both nonpolarized cell lines and four different, clinically relevant epithelia. Since polarization is critical to the apical targeting of CFTR (60,61), differentiation of epithelia was verified by immunolocalization of tight junctional (ZO-1 and occludin) and lateral membrane markers (E-cadherin) and by domain-specific lectin labeling as well. Adverse effects of lipid-mediated transfection were also ruled out by generating stably transfected PANC-1 epithelia and by using retroviral infection (HTE, MDCK, and CaCo-2 epithelia).…”

Section: Discussionmentioning

confidence: 99%

The Role of the C Terminus and Na+/H+ Exchanger Regulatory Factor in the Functional Expression of Cystic Fibrosis Transmembrane Conductance Regulator in Nonpolarized Cells and Epithelia

Benharouga

Sharma

et al. 2003

Journal of Biological Chemistry

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The conserved C-terminal peptide motif ( 1476 DTRL) of the cystic fibrosis transmembrane conductance regulator (CFTR) ensures high affinity binding to different PSD-95/Disc-large/zonula occludens-1 (PDZ) domaincontaining molecules, including the Na ؉ /H ؉ exchanger regulatory factor (NHERF)/ezrin-radixin-moesin-binding phosphoprotein of 50 kDa. The physiological relevance of NHERF binding to CFTR is not fully understood. Individuals with mutations resulting in premature termination of CFTR (S1455X or ⌬26 CFTR) have moderately elevated sweat Cl ؊ concentration, without an obvious lung and pancreatic phenotype, implying that the CFTR function is largely preserved. Surprisingly, when expressed heterologously, the ⌬26 mutation was reported to abrogate channel activity by destabilizing the protein at the apical domain and inducing its accumulation at the basolateral membrane

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Targeting of CFTR protein is linked to the polarization of human pancreatic duct cells in culture

Cited by 22 publications

References 30 publications

ΔF508 CFTR protein expression in tissues from patients with cystic fibrosis

ΔF508 CFTR protein expression in tissues from patients with cystic fibrosis

CFTR interacts with ZO-1 to regulate tight junction assembly and epithelial differentiation via the ZONAB pathway

The Role of the C Terminus and Na+/H+ Exchanger Regulatory Factor in the Functional Expression of Cystic Fibrosis Transmembrane Conductance Regulator in Nonpolarized Cells and Epithelia

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