protein translocation

Ian A. York iayork at
Fri Dec 6 10:30:09 EST 1996

In article <Pine.SUN.3.91.961205172820.12366A-100000 at gc>,
Mazen Saleh  <saleh at> wrote:
>does anyone know of an example where the ER protein translocation
>complex works in reverse. i.e translocate a protein from inside
>the ER to the cytoplasmic side?. I need an example, preferably,
>of an endogenous cellular protein.

I know of no examples that exactly fit your criteria, but I can think of a
couple that almost fit.  First, there's a well-known but poorly defined
pathway whereby peptides and/or proteins can leave the ER and become
degraded.  This has been shown in antigen processing assays in a number of
ways.  The route by which this proteins/ peptides leave the ER is not
known, except that it isn't the TAP transporter complex.  The ER protein
translocation machinery is still one candidate, though only because
nothing else has been excluded.

The other example was first (I think) clearly described by Hidde Ploegh's
lab. In humans cells infected with HCMV the class I MHC heavy chain is
very rapidly shunted back out of the ER and is rapidly degraded.  Based on
the speed of this, it's plausible that the protein never has a chance to
leave the translocation machinery, so it may be 'simply' falling back out. 
More recently a very similar phenomenon was described by some other group
in JBC - sorry, I can't remember the authors; it was within the last
couple of months.  In this case the cells were uninfected and involved
several proteins, and the authors suggessted that this was a general
pathway that is important in degradation of ER proteins. 

It seems to me that ER proteins in the cytoplasm are likely to be degraded
very rapidly - the environment in the cytoplasm must be fairly hostile to
an ER protein, and it's likely to become misfolded and hence degraded.
For that reason it may be difficult to track those proteins which go from
the ER to the cytoplasm.

      Ian York   (iayork at  <>
      "-but as he was a York, I am rather inclined to suppose him a
       very respectable Man." -Jane Austen, The History of England

More information about the Cellbiol mailing list