ArticleThe Biochemical journal2001
Multiple endocytic signals in the C-terminal tail of the cystic fibrosis transmembrane conductance regulator.
Article in The Biochemical journal, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 53 citations in OpenAlex.
- Regulation of CFTR stability at the plasma membrane-Mechanisms and therapeutic opportunities in cystic fibrosis.FEBS letters · 2026Review
- Functional characterization of endocytic signals in the SynDIG/PRRT family members SynDIG1 and SynDIG4 in heterologous cells and neurons.Frontiers in cellular neuroscience · 2024Article
- Cell type-specific regulation of CFTR trafficking-on the verge of progress.Frontiers in cell and developmental biology · 2024Review
- Transcytosis maintains CFTR apical polarity in the face of constitutive and mutation-induced basolateral missorting.Journal of cell science · 2019Article
- From the endoplasmic reticulum to the plasma membrane: mechanisms of CFTR folding and trafficking.Cellular and molecular life sciences : CMLS · 2017Review
- A sequence upstream of canonical PDZ-binding motif within CFTR COOH-terminus enhances NHERF1 interaction.American journal of physiology. Lung cellular and molecular physiology · 2016Article
- A C-terminal tyrosine-based motif in the bile salt export pump directs clathrin-dependent endocytosis.Hepatology (Baltimore, Md.) · 2012Article
- Disabled-2 protein facilitates assembly polypeptide-2-independent recruitment of cystic fibrosis transmembrane conductance regulator to endocytic vesicles in polarized human airway epithelial cells.The Journal of biological chemistry · 2012Article
- Dab2 is a key regulator of endocytosis and post-endocytic trafficking of the cystic fibrosis transmembrane conductance regulator.The Biochemical journal · 2012Article
- A role of the sulfonylurea receptor 1 in endocytic trafficking of ATP-sensitive potassium channels.Traffic (Copenhagen, Denmark) · 2011Article
- Alpha-AP-2 directs myosin VI-dependent endocytosis of cystic fibrosis transmembrane conductance regulator chloride channels in the intestine.The Journal of biological chemistry · 2010Article
- MinK-dependent internalization of the IKs potassium channel.Cardiovascular research · 2009Article
- Structural and functional divergence of two fish aquaporin-1 water channels following teleost-specific gene duplication.BMC evolutionary biology · 2008Article
- CFTR surface expression and chloride currents are decreased by inhibitors of N-WASP and actin polymerization.Biochimica et biophysica acta · 2007Article
- Endocytic trafficking of CFTR in health and disease.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2007Review
- Endocytic trafficking routes of wild type and DeltaF508 cystic fibrosis transmembrane conductance regulator.Molecular biology of the cell · 2004Article
- The dopamine transporter constitutively internalizes and recycles in a protein kinase C-regulated manner in stably transfected PC12 cell lines.The Journal of biological chemistry · 2003Article
- Effects of C-terminal deletions on cystic fibrosis transmembrane conductance regulator function in cystic fibrosis airway epithelia.Proceedings of the National Academy of Sciences of the United States of America · 2003Article
- Functional analysis of the C-terminal boundary of the second nucleotide binding domain of the cystic fibrosis transmembrane conductance regulator and structural implications.The Biochemical journal · 2002Article
- COOH-terminal truncations promote proteasome-dependent degradation of mature cystic fibrosis transmembrane conductance regulator from post-Golgi compartments.The Journal of cell biology · 2001Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-dependent protein kinase (PKA)-activated chloride channel that is localized to the plasma membrane and endosomal compartment. Endosomal targeting of CFTR is attributed to the Tyr(1424)-based internalization signal, identified in the C-terminal tail of the channel. Mutation of the Tyr(1424) residue could partly inhibit the endocytosis of CFTR and its association with the adapter protein AP-2. To reveal additional endosomal targeting signals, site-directed mutagenesis of both a chimaera, composed of a truncated form of interleukin 2 receptor alpha chain (TacT) and the C-terminal tail of CFTR (Ct), and the full-length CFTR was performed. Morphological and functional assays revealed the presence of multiple internalization motifs at the C-terminus, consisting of a phenylalanine-based motif (Phe(1413)) and a bipartite endocytic signal, comprising a tyrosine (Tyr(1424)) and a di-Leu-based (Leu(1430)-Leu) motif. Whereas the replacement of any one of the three internalization motifs with alanine prevented the endocytosis of the TacT-Ct chimaera, mutagenesis of Phe(1413)-Leu impaired the biosynthetic processing of CFTR, indicating that Phe(1413) is indispensable for the native structure of CFTR. In contrast, replacement of Leu(1430)-Leu- and Tyr(1424)-based signals with alanine increased the cell-surface density of both the chimaeras and CFTR in an additive manner. These results suggest that the internalization of CFTR is regulated by multiple endocytic sorting signals.
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