Early Events in Secretion of Main Milk Proteins: Occurrence of Precursors

Abstract A cell can synthesize hundreds of proteins that must find their way to appropriate places within the cytoplasm or beyond. This suggests that newly manufactured proteins are dispatched to their proper destinations through a sophisticated transportation network, and we are only beginning to decipher the chemical “zip code system” which is operating (Figure 1). It was recognized early that secretary proteins including lactoproteins (23, 24, 25) are synthesized on ribosomes attached through their large subunits to the membrane of the endoplasmic reticulum (ER) and are vectorially discharged into the ER intraluminal space. However, mechanisms in selecting specific messenger-RNAs (mRNAs) for translation on membrane-bound polysomes and transferring the newly synthesized polypeptide chains through ER membranes were not known. It first was thought that there were two types of ribosomes in terms of structure, but this concept finally was dismissed because of lack of evidence (reviewed in 63, 77). In the early 1970's, Blobel and Sabatini's proposal (6) that binding of functioning ribosomes might be induced by the nascent polypeptide chains themselves was substantiated by the discovery of precursors of immunoglobunlin light chains (59) with short-lived amino terminal sequences through to be the signalling devices whereby segreation of ribosomes and secretory protein is achieved.