CFTR: Difference between revisions
No edit summary |
mNo edit summary |
||
| Line 1: | Line 1: | ||
CFTR regulates ion concentration in extracellular fluid due to its role as a plasma membrane Cl channel in [[Epithelial cells|epithelial cells]] <ref>Alberts, Bruce (2002), Molecular Biology Of The Cell, 4th edition, Garland Science</ref>. | CFTR regulates ion concentration in extracellular fluid due to its role as a plasma membrane Cl channel in [[Epithelial cells|epithelial cells]] <ref>Alberts, Bruce (2002), Molecular Biology Of The Cell, 4th edition, Garland Science</ref>. | ||
CFTR is the name commonly given to the gene responsible for the production of the [[Cystic fibrosis|Cystic Fibrosis]] Transmembrane Regulator [[Proteins|protein]]. This [[Gene|gene]], when mutated, can cause [[Cystic fibrosis|cystic fibrosis]], although it is [[Recessive gene|recessive]], whether the mutations are identical or not. So far, over 1500 mutations of the [[CFTR|CFTR]] gene have been discovered, the most common being the ∆F508 mutation, sometimes in as few as one individual. Some of the other more common mutations include; ΔF508 G542X G551D N1303K and W1282X. In the ∆F508 mutation a [[Phenylalanine|phenylalanine]] residue at amino acid 508 has been deleted and so the channel is no longer functional <ref>Alberts, Bruce (2002), Molecular Biology Of The Cell, 4th edition, Garland Science</ref>. This mutation is a class II mutation where abnormal processing occurs in the [[Endoplasmic reticulum|endoplasmic reticulum]]. The [[Protein|protein]] is not recognised and is degraded via [[Ubiquitin|ubiquitin]] tagging. | CFTR is the name commonly given to the gene responsible for the production of the [[Cystic fibrosis|Cystic Fibrosis]] Transmembrane Regulator [[Proteins|protein]]. This [[Gene|gene]], when mutated, can cause [[Cystic fibrosis|cystic fibrosis]], although it is [[Recessive gene|recessive]], whether the mutations are identical or not. So far, over 1500 mutations of the [[CFTR|CFTR]] gene have been discovered, the most common being the ∆F508 mutation, sometimes in as few as one individual. Some of the other more common mutations include; ΔF508 G542X G551D N1303K and W1282X. In the ∆F508 mutation a [[Phenylalanine|phenylalanine]] residue at amino acid 508 has been deleted and so the channel is no longer functional <ref>Alberts, Bruce (2002), Molecular Biology Of The Cell, 4th edition, Garland Science</ref>. This mutation is a class II mutation where abnormal processing occurs in the [[Endoplasmic reticulum|endoplasmic reticulum]]. The [[Protein|protein]] is not recognised and is degraded via [[Ubiquitin|ubiquitin]] tagging. | ||
| Line 7: | Line 7: | ||
CFTR is a passive transporter and it is special in the [[ABC Superfamily|ABC superfamily]] proteins. It has got 12 transmembrane domains, with two nucleotide binding domains (NBD1 and NBD2) and a regulatory domain. The binding of [[ATP|ATP is]] essential for the function for the channel, NBD1 and NBD2 both bind [[ATP|ATP]] however only NBD2 can hydrolyse [[ATP|ATP]].<br> | CFTR is a passive transporter and it is special in the [[ABC Superfamily|ABC superfamily]] proteins. It has got 12 transmembrane domains, with two nucleotide binding domains (NBD1 and NBD2) and a regulatory domain. The binding of [[ATP|ATP is]] essential for the function for the channel, NBD1 and NBD2 both bind [[ATP|ATP]] however only NBD2 can hydrolyse [[ATP|ATP]].<br> | ||
[[Cystic fibrosis|Cystic Fibrosis]] is a disease condition caused by several mutations in the [[Gene|gene]] encoding CFTR protein, which functions as a Cl<sup>-</sup> channel in the [[Plasma membrane|plasma membrane]] of epithelial cells. The CFTR channel plays a particularly important role especially in the [[Lungs|lungs]] - where it controls certain ion concentrations found in the extracellular fluid <ref>Alberts | [[Cystic fibrosis|Cystic Fibrosis]] is a disease condition caused by several mutations in the [[Gene|gene]] encoding CFTR protein, which functions as a Cl<sup>-</sup> channel in the [[Plasma membrane|plasma membrane]] of epithelial cells. The CFTR channel plays a particularly important role especially in the [[Lungs|lungs]] - where it controls certain ion concentrations found in the extracellular fluid <ref>Alberts <i>et al.</i>; (2008) Molecular Biology of the Cell 5th ed. p.666. Garland Science</ref>. The disease causes decreased chloride concentration in the airway which leads to the thickening of the gel layer. As it thickens it becomes too heavy for the cilia to brush it along and so sticks to the cilia. Many organs become affected by [[Cystic fibrosis|Cystic Fibrosis]], which disrupts their normal functioning. A major problem is encountered in the [[Lung|lungs]], where there is clogging of the [[Bronchial passage|bronchial passage]] and infection. Consequently those factors impede breathing and [[Lung|lungs]] are slowly destroyed. In [[Liver|liver]], disease affects digestion, as it plugs in the small [[Bile duct|bile ducts]]. [[Organ|Organs]] which are altered by the disease are also [[Pancreas|pancreas]], [[Small intestine|small intestine]] and the [[Reproductive duct|reproductive duct]].<br> | ||
=== References === | === References === | ||
<references /> | <references /> | ||
Revision as of 17:44, 15 November 2011
CFTR regulates ion concentration in extracellular fluid due to its role as a plasma membrane Cl channel in epithelial cells [1].
CFTR is the name commonly given to the gene responsible for the production of the Cystic Fibrosis Transmembrane Regulator protein. This gene, when mutated, can cause cystic fibrosis, although it is recessive, whether the mutations are identical or not. So far, over 1500 mutations of the CFTR gene have been discovered, the most common being the ∆F508 mutation, sometimes in as few as one individual. Some of the other more common mutations include; ΔF508 G542X G551D N1303K and W1282X. In the ∆F508 mutation a phenylalanine residue at amino acid 508 has been deleted and so the channel is no longer functional [2]. This mutation is a class II mutation where abnormal processing occurs in the endoplasmic reticulum. The protein is not recognised and is degraded via ubiquitin tagging.
CFTR is a member of the ABC superfamily of proteins and is the only Cl- channel in this family. It is very similar to P-glycoprotein, apart from the fact that CFTR contains a large regulatory domain (R domain). The CFTR gene was cloned in 1989.
CFTR is a passive transporter and it is special in the ABC superfamily proteins. It has got 12 transmembrane domains, with two nucleotide binding domains (NBD1 and NBD2) and a regulatory domain. The binding of ATP is essential for the function for the channel, NBD1 and NBD2 both bind ATP however only NBD2 can hydrolyse ATP.
Cystic Fibrosis is a disease condition caused by several mutations in the gene encoding CFTR protein, which functions as a Cl- channel in the plasma membrane of epithelial cells. The CFTR channel plays a particularly important role especially in the lungs - where it controls certain ion concentrations found in the extracellular fluid [3]. The disease causes decreased chloride concentration in the airway which leads to the thickening of the gel layer. As it thickens it becomes too heavy for the cilia to brush it along and so sticks to the cilia. Many organs become affected by Cystic Fibrosis, which disrupts their normal functioning. A major problem is encountered in the lungs, where there is clogging of the bronchial passage and infection. Consequently those factors impede breathing and lungs are slowly destroyed. In liver, disease affects digestion, as it plugs in the small bile ducts. Organs which are altered by the disease are also pancreas, small intestine and the reproductive duct.