|MadSci Network: Medicine|
There are many, many diseases associated with missing, mutant or misregulated membrane transport systems. Probably the best known is CFTR (cystic fibrosis transmembrane regulator). This is a chloride ion channel of most epithelial cells in the body. About half of CF patients have an identical mutation that prevents the protein from folding properly during its synthesis. Because it is misfolded, the cell recognizes the "damaged" protein and degrades it. It therefore never reaches the cell membrane. Without this chloride channel, epithelial cells cannot properly regulate chloride transport which secondarily causes severe problems with sodium and water transport/secretion. In the lung, this leads to very thick mucus in the alveolae that cannot be cleared, thus plugging the lungs and providing a very nice growth environment for bacteria, particularly Pseudomonas aeruginosa and Burkholderia cepacia. CF patients eventually die from suffocation, brought on by recurring bacterial infections that damage the lungs irreversibly over time. Virtually every cell membrane transport system known, when mutated, can cause disease, some very severe, some not so severe. As a prime example, has been elegantly worked out in the kidney by Rick Lifton and colleagues at Yale University. Dr. Lifton has discovered mutations in several different types of transporters all along the kidney nephron. The disease and its consequences depend not only on the particular transporter involved, but where along the length of the nephron that particular transporter is expressed. A good place to start would be a recent review by Lifton,R.P., Gharavi,A.G., and Geller,D.S. "Molecular mechanisms of human hypertension", Cell 104:545-556(2001). I would note also that it doesn't have to be a mutation in a transporter. Many examples are known where mutations in a membrane hormone receptor causes a problem.
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