Mechanisms for the incorporation of proteins in membranes and organelles

Because of the high degree of organizational complexity of eucaryotic cells, it is clear that the implementation of their genetic programs must, in many cases, involve a complex sequence of cotranslational and posttranslational events that are necessary to transfer polypeptides from their sites of synthesis to their sites of function. It is difficult to envisage the existence of a single general mechanism that would ensure that all polypeptides released from ribosomes attain their correct subcellular destination . This is because there are, in a eucaryotic cell, at least as many possible destinations for a newly synthesized polypeptide as there are different compartments and membrane systems. Moreover, it is not likely that completed and fully folded polypeptides, with their charged and polar residues exposed to the aqueous environment, could freely traverse hydrophobic barriers constituted by phospholipid bilayers, which are the universal feature of all cell membranes (208). Instead, it may be expected that special mechanisms have evolved that direct polypeptides to specific membranes and, when necessary, assist them in their passage across the hydrophobic barriers . These mechanisms must involve specific receptors for structural features ofthe polypeptides and may entail conformational changes or even extensive structural modifications of the polypeptide, as well as the expenditure of energy . In this paper we consider mechanisms for the transfer of newly synthesized polypeptides to their sites of function in different subcellular membranes and organelles, and discuss models in which specific features ofthe polypeptides serve as signals to direct them along selected subcellular pathways to their final destination . These signals may act during translation or after synthesis of the polypeptide is completed and may or may not be removed from the initial product of translation . Transient or permanent signals within polypeptides destined to membranes would also account for the final characteristic orientation of membrane proteins with respect to the phospholipid bilayer . Several other reviews discussing various aspects of this subject have recently appeared (15, 44, 53, 117a, 127, 243a) .