MadSci Network: Cell Biology

Re: how do proteins move through the cell?

Date: Fri Jul 21 10:23:06 2000
Posted By: Michael Maguire, Faculty,Case Western Reserve Univ.
Area of science: Cell Biology
ID: 964115665.Cb

1.  Actually, the cell really is extremely crowded.  Your library will 
likely have a copy of "The Machinery of Life" by David S. Goodsell 
(Springer-Verlag, 1992).  Goodsell draws cells and cell components to 
scale and based on real data.  The cover alone ought to convince you how 
crowded a cell is.

Now to protein trafficking.  

2.  Soluble proteins.  Soluble proteins destined for the cytosol are 
simply synthesized and possibly directly released off the endoplasmic 
reticulum (ER).  Those that are modified by addition of carbohydrate or 
lipid may sometime go to the Golgi apparatus through the soluble interior 
of the ER which is directly connected to the soluble space of the Golgi.  
However, they can usually be modified directly by soluble enzymes.

3.    Membrane proteins.  Membrane proteins are inserted into the ER 
membrane AS THEY ARE BEING MADE.  They achieve their final 
conformation/topology while in the ER, or at least a topology very close 
to final.  They then move laterally through the ER membrane to the Golgi.  
This likely involves interactions with some set of cytoskeletal components 
that act as attachment points and motors.  Once in the Golgi, they get 
modified if that's what that particular protein needs.  

     How do the various membrane proteins get to their respective 
organelles?  For the most part, membrane proteins appear to have specific 
short amino acids sequences that direct that protein to a particular 
organ.  For example, a sequence for translocation to the nucleus is 5 a.a. 
in length and contains all aspartates and glutamates.  Other signals are 
present which will send a protein to a mitochondrion or back to the ER, 

       In the Golgi, proteins bound, for example, to the mitochondrion end 
up being sorted out as they pass through the various layers of the Golgi 
until they are together.  Once together and when they have reached the 
final membranes of the Golgi, they "bud" off as a vesicle.  The 
localization signal of the proteins appears to somehow tell the machinery 
to take that vesicle to the mitocondrion where it fuses and thus inserts 
new protein into the membrane.  Localization signals may or may not 
(usually) be cleaved off.

    Switching the short localization sequence on a protein from, for 
example, nucleus to mitochondrial will cause that protein to be directed 
to the wrong organ where it may or may not function properly or possibly 
even be toxic.

4.   Now finally to bacteria.  Membrane proteins in a bacterium are 
inserted into the membrane DURING SYNTHESIS.  If, for example, amino acids 
10-30 form a membrane domain, that segment is being inserted into the 
membrane by the time the ribosome has attached a.a. 40 or 45.  For insight 
into the insertion process, see Heinrich et al., Cell (2000) 102:233-244.

  How are they sorted?  Good question.  We don't know for most proteins 
but the answer I think everyone assumes is that localization to a 
particular part of the cell is due to specific protein-protein 
interactions.  This is however quite dynamic and localization can change 
very quickly.  

   For insertion into the outer membrane, the same machinery that inserts 
proteins into the plasma/cell membrane probably takes outer membrane 
proteins also but there is an additional component(s) (probably) that help 
guide insertion into the outer membrane (of the Gram negatives).  I 
suspect that the machinery used for this purpose has somehow been coopted 
by evolution to form the Type III secretion systems (there are 4 systems 
known) that pathogenic bacteria use to insert proteins not only through 
their inner and outer membranes but directly into the plasma membrane or 
even into the cytosol of the cell they are invading.  For a general review 
of secretion systems use PubMed or some other search program and find 
reviews by Tony Pugsley.  For some insight into the various specific 
proteins and some good pictures, see papers by Joe Lutkenhaus, Piet de 
Boer, Janine Maddock and Lucy Shapiro in addition to Pugsley.

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