How do proteins know where they belong

There are several hypotheses for this question, which again need not be mutually exclusive.

ER-resident proteins are prevented from moving with this bulk flow by a special sorting signal (KDEL) which is also responsible for their transport from the GoLGl-apparatus back to the ER, should they accidentally move to the GoLGl-apparatus. Proteins not bearing this signal will automatically move with the bulk flow from the rER to the GoLGl-apparatus.

Proteins may form large oligomeric complexes with other proteins in the compartment where they belong. These complexes could be too big to be included into transport vesicles. Such aggregation can be demonstrated experimentally: If one of the sugar transferases from the median-GoLGl is fused with a protein bearing an ER retention signal, this enzyme will accumulate in the

ER instead of being transported to the Golgi. But it will also retain other transferases which have not been manipulated, and in such a mutant cell the Golgi apparatus will be very small or even non-existent. Formation of such complexes is made easier by the fact that most GoLGl-proteins have a very similar structure, an N-terminal cytoplasmic domain, a single transmembrane domain (where complex formation occurs) and a C-terminal catalytic domain facing the lumen of the cisterna.

Another hypothesis starts with the observation that the concentration of cholesterol in the membrane increases from ER over Golgi to plasma membrane. This leads to an increase in the thickness of the membranes in the same order. The transmembrane domains of Golgi proteins are slightly shorter than their counterparts in plasma membrane proteins. If such a protein were to be brought into the plasma membrane, hydrophilic sidechains from the cytoplas-mic or external domains would be drawn into the hydrophobic membrane environment, which is energetically unfavourable.

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