CFTR Membrane Protein Introduction

Introduction of CFTR

Cystic fibrosis transmembrane conductance regulator (CFTR) is also known as ATP-binding cassette sub-family C member 7, channel conductance-controlling ATPase or cAMP-dependent chloride channel. The CFTR gene encodes a cAMP-regulated chloride channel protein present in the apical membrane of epithelial cells. CFTR follows the same domain structure as other ABC transporters: two nucleotide-binding domains (NBD) in tandem with two transmembrane domains (TMD). It differs from other transporters by its regulatory region or 'R' region. The R region is located between the first TMD and the second NBD within the cytoplasm.

Function of CFTR Membrane Protein

CFTR is unique among ABC transporters because it is the only member of the membrane protein family to act as an ion channel member. CFTR was originally thought to be specifically expressed by epithelial cells. However, recent studies have shown that CFTR is expressed in neurons of human central nervous system, including the brain and spinal cord. In addition, the widespread presence of CFTR has been demonstrated in the peripheral nervous system, including the human spinal cord, sympathetic nerves, and cervical ganglia. These findings suggest that CFTR plays an important role in the physiology of the central and peripheral nervous systems. CFTR may participate in neuronal physiology through several mechanisms, with the most important of which is: maintaining intracellular electrolyte homeostasis, regulating membrane recycling, modulating membrane traffic, governing the efflux of glutathione, regulating neuropeptide secretion, and acting as a neuromodulator and cell signaling molecule.

Fig.1 Homology models for CFTR. (Meng, 2017)

Application of CFTR Membrane Protein in Literature

1. Li X., et al. Retinoic acid promotes stem cell differentiation and embryonic development by transcriptionally activating CFTR. Biochim Biophys Acta. 2018, 1865(4): 605-15. PubMed ID: 29326073
   
   

   This study found an important role of CFTR in mediating RA-dependent signaling in stem cell differentiation and embryo development.

2. Zhao D., et al. Association between F508 deletion in CFTR and chronic pancreatitis risk. Dig Liver Dis. 2017, 49(9): 967-72. PubMed ID: 28780053
   
   

   This article revealed that CFTR had been reported to affect individual susceptibility to chronic pancreatitis (CP). F508 deletion in CFTR was a risk factor for CP, while Indians with F508 deficiency had much higher CP morbidity.

3. Bossmann M., et al. Signaling Cascade Involved in Rapid Stimulation of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) by Dexamethasone. Int J Mol Sci. 2017, 18(8). pii: E1807. PubMed ID: 28825630
   
   

   This article verified that Dexamethasone could induce a rapid stimulation of CFTR activity, which was dependent on PI3K/AKT signaling in airway epithelial cells.

4. Tu Z., et al. CFTR is a potential marker for nasopharyngeal carcinoma prognosis and metastasis. Oncotarget. 2016, 7(47): 76955-65. PubMed ID: 27769067
   
   

   The results showed that CFTR was down-regulated in nasopharyngeal carcinoma (NPC) tissues and cell lines, and that low expression levels of CFTR were associated with cancer progression and poor survival in NPC patients. Furthermore, this study demonstrated that CFTR manipulation in NPC cell lines affected cell migration and invasion and provided a molecular basis for the role of CFTR in NPC development.

5. Xue R., et al. Expression of Cystic Fibrosis Transmembrane Conductance Regulator in Ganglia of Human Gastrointestinal Tract. Sci Rep. 2016, 6: 30926. PubMed ID: 27491544
   
   

   This study of gastrointestinal samples revealed extensive expression of CFTR in the intestinal ganglia, suggesting that CFTR may play a role in the physiology of the innervation of the gastrointestinal tract.

CFTR Preparation Options

Membrane protein studies have advanced significantly over the past few years. Based on our versatile Magic™ membrane protein production platform, we could offer a series of membrane protein preparation services for worldwide customers in reconstitution forms or membrane protein mutants. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-CFTR antibody development services.

• Magic™ Membrane Protein Production Platform
• Magic™ Anti-Membrane Protein Antibody Discovery Platform

During the past years, Creative Biolabs has successfully generated many functional membrane proteins for our global customers. We are happy to accelerate the development of our clients’ programs with our one-stop, custom-oriented service. For more detailed information, please feel free to contact us.

Reference

1. Meng X, et al. (2017). The cystic fibrosis transmembrane conductance regulator (CFTR) and its stability. Cell Mol Life Sci. 74(1): 23-38.

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