At least in the case of Cystic Fibrosis it happens that a mutant protein (which could actually function!) is held in the ER because the ER detects it as misfolded. Does this happen in every type of mutant protein?

If so, should I conclude that such genetic disorders are caused because of the total absence of a protein rather than because of a misfolded protein? If not, why would the ER or anything else in the cell allow some mutated proteins to do any job (Like in the case of Sickle cell anaemia, where an amino acid substitution happens)?

How do scientists conclude that a misfolded protein could have done a good enough job (Like in the case of cystic fibrosis)?


1 Answer 1


Membrane proteins have to go to the ER from where they are transported to the Golgi apparatus. Usually these proteins are translocated into the ER while translation is still going on. There are chaperones (such as calbindin) in ER which help in translocation and also catalyze initial steps of folding. ER is also involved in unfolded protein response. Unless the protein is properly folded it is not transported to Golgi. However, this process is regulated at many steps and I wont add a detailed explanation of the mechanism, in this answer.

To conclude ER is involved in this case because the protein considered is a membrane protein.

  • $\begingroup$ If we assume that the process which checks whether the protein is properly folded has nothing wrong, then is it safe to assume that all genetic disorders in proteins which are checked by the system happen because of the absence of those proteins (which will be held in ER) rather than because of a misfolded protein allowed to function ? $\endgroup$
    – biogirl
    Commented Sep 4, 2013 at 16:44
  • $\begingroup$ misfolded proteins can themselves be toxic to the cells and that is why their rapid folding or clearance is important. Sometimes the protein synthesis can overwhelm the folding ability of the cell which may cause the accumulation of the former. Plus, a mutated protein may simply be difficult to fold. And, ER is not the only site for protein folding. Cytosolic proteins fold with the assistance of cytosolic chaperones (Hsps) $\endgroup$
    Commented Sep 5, 2013 at 10:54

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