cystic fibrosis

[Cristagali]

Where does the CF protein get jammed up? ER or GB? I've seen conflicting info. Thanks.

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[nuclearrabbit77]

the problem is a loss of function of cAMP-dependent kinase activation of the chloride channel. the protein is correctly translated and there are no problems in cell trafficking and localization to the cell membrane.

 

[lindyloohoo]

this makes it impossible for the cell to pump OUT chloride right? with chloride not moving out then water can't move out, which is why the secretions are viscous, right? I just realized today (after listening to everyone talk about how pathophys is important) that I have no clue why the secretions were viscous.

 

[nuclearrabbit77]

yup thats right. in the sweat glands, it's flipped around though, with it unable to reabsorb chloride to make the normally hypotonic sweat. mmmm. salty baby.

 

[Idiopathic]

Not true...the protein is degraded in the Golgi, as far as I know.

 

[nuclearrabbit77]

Not true...the protein is degraded in the Golgi, as far as I know.

yah, i bungled that one up. yes, you are right, it is degraded before it reaches the cell membrane. i did some research and it's normally degraded
in the ER....the mutation does cause decreased cAMP/PKA response when expressed in patch-clamp experiments.


http://www.ncbi.nlm.nih.gov/entrez/...ve&db=PubMed&list_uids=10790148&dopt=Abstract

 

[Cristagali]

Thanks guys, but you see my problem here. Both of you told me two different places. Idio says GB, Nuclear says ER. The CFTR protein dysfunction is due to misfolding, that is, the chaperone responsible for folding the CFTR protein will NOT release the CFTR protein, thus causing misfolding. So... is the CFTR protein misfolded in the ER and then stopped in the GB? or is it stopped in the ER??

 

[nuclearrabbit77]

http://www.ncbi.nlm.nih.gov/entrez/...eve&db=PubMed&list_uids=7553863&dopt=Abstract

it's marked for ubiquitin-dependent degradation in the ER.

 

[Jalby]

You are all wrong. And right. There are a couple of hundred different CF mutations. They get stuck in all different places (golgi, degraded, get to surface but isn't quite function, etc, etc) Hence, the many different phenotypes for CF.

Now, the original question should probably be changed to, what is the defect in the most common type of CF which I think is the deletion of one amino acid at number 508. That, someone else will have to look up because I'm to lazy.

 

[nuclearrabbit77]

you're right jalby, i was assuming we were talking about the delta F508 polymorphism. it's 70% of cases.

 

[Cristagali]

Yes, my original question assumed that you all were "mind readers", my apologies. Jalby states it best. That seems to be the one a board question can come out of, so I will try to once and for all, figure out if the mutated Phe 508 CFTR stops in ER or not. PS Are Ubiquitan, HSP 70, chaperone, all the same?? Thanks

 

[nuclearrabbit77]

http://www.tulane.edu/~biochem/med/hsp.htm

review of HSP. essentially it's a family of proteins that is heat inducible, and a subset of them participate in molecular chaperone (protein folding/regulation).



ubiquitin is a molecular marker put on proteins that are labeled to be destroyed at the proteasome (a big recycle/trash bin)

http://www.med.nyu.edu/Path/Pagano/ubiq_prot.html