Sorry, you need to enable JavaScript to visit this website.

CFTR Protein Synthesis: The making of a normal CFTR protein channel

The CFTR protein reaches the apical epithelial cell membrane as part of a multistep process. As with all protein, this process involves synthesis (transcription and translation), folding and processing, trafficking to their destination (e.g., apical cell membrane), and turnover.1-4

CFTRprotein synthesis

CFTR protein life cycle

CFTR protein synthesis1

  • In the nucleus, the CFTR gene is transcribed into mRNA
  • Introns are then removed from mRNA in a process called splicing
  • The CFTR protein is synthesized in the cytoplasm and enters the endoplasmic reticulum (ER) during synthesis

CFTR protein folding and processing2-4

  • Immature CFTR protein is folded and processed in the ER
  • Any protein that does not fold properly is degraded

CFTR protein trafficking2,4

  • Mature CFTR protein is transported to the Golgi apparatus for final processing and the mature protein is then trafficked to the cell surface

CFTR protein function5,6

  • At the cell surface, CFTR proteins function as channels that transport chloride and bicarbonate ions

CFTR protein turnover3

  • CFTR channels have a limited lifespan and are eventually removed in a process called turnover

When protein synthesis, folding and processing, and trafficking occur properly, fully functional CFTR proteins reach the cell surface in sufficient quantity to maintain adequate ion transport.1-3,5

What contributes to the function of CFTR proteins once they reach the cell surface? Learn more.

    References:
  1. Strachan T, Read AP. Chapter 1: DNA structure and gene expression. In: Human Molecular Genetics. 2nd ed. New York, NY: Wiley‐Liss; 1999. http://www.ncbi.nlm.nih.gov/books/NBK7585. Accessed October 20, 2014.
  2. Cooper GM. Chapter 9: Protein sorting and transport. In: The Cell: A Molecular Approach. 2nd ed. Washington, DC: ASM Press; 2000.
  3. Ward CL, Kopito RR. Intracellular turnover of cystic fibrosis transmembrane conductance regulator. J Biol Chem. 1994;269(41):25710-25718.
  4. Mall M, Kreda SM, Mengos A, Jensen TJ, et al. The DeltaF508 mutation results in loss of CFTR function and mature protein in native human colon. Gastroenterology. 2004;126(1):32-41.
  5. Zielenski J. Genotype and phenotype in cystic fibrosis. Respiration. 2000;67(2):117‐133.
  6. Welsh MJ, Ramsey BW, Accurso F, Cutting GR. Cystic fibrosis: membrane transport disorders. In: Valle D, Beaudet A, Vogelstein B, et al, eds. The Online Metabolic & Molecular Bases of Inherited Disease. The McGraw‐Hill Companies Inc; 2004:part 21, chap 201. www.ommbid.com.