Lysosomes protein entry into

Neville, D. M. Jr., Chang, T. M. Receptor mediated protein transport into cells. Entry mechanisms for toxins, hormones, antibodies viruses, lysosomal hydrolases, asialoglycoprotdns and carrier proteins, in Current Topics in Membranes and Transport, (eds.) Kleinzeller, A., Bron-ner, C., p. 65, New York, Acad. Press 1978 Roberts, A. V. S. et al. Biochem. J. 160, 621 (1967)... 

Studies with various actinides, following their injection into experimental animals, have shown that after entry into the cells of liver, spleen, kidney and testes, and probably also in other tissues, the metals interact with the subcellular organelles and with the intracellular proteins (Duffield and Taylor 1986). Immediately after entry into the cell the actinides react first with the cytosolic proteins and are then transferred into the membrane-bounded lysosomes within the cell. The rate of transfer to the lysosomes is fastest for americium and curium and slowest for plutonium. In rat or hamster liver plutonium is associated first with an unidentified protein - Protein X -with a molecular mass of 150 (hamster) and 200 kDa (rat) (Neu-Mueller 1988), and then subsequently with the iron-storage protein ferritin. In contrast, americium and curium are rapidly bound to ferritin, without any apparent binding to protein X. Within the lysosomes ferritin appears to be the important binding species (Duffield and Taylor 1986). Much less is known concerning the subcellular distribution of lanthanides, but comparative studies using and Np, Pu and Am confirm the importance of the lysosomes as a deposition site for lanthanides and actinides (Seidel et al. 1986). 

Substrate availability to the cell is affected by the supply of raw materials from the environment. The plasma membranes of cells incorporate special and often specific transport proteins (translocases) or pores that permit the entry of substrates into the cell interior. Furthermore pathways in eukaryotic cells are often compartmentalized within cytoplasmic organelles by intracellular membranes. Thus we find particular pathways associated with the mitochondria, the lysosomes, the peroxisomes, the endoplasmic reticulum for example. Substrate utilization is limited therefore by its localization at the site of need within the cell and a particular substrate will be effectively concentrated within a particular organelle. The existence of membrane transport mechanisms is crucial in substrate delivery to, and availability at, the site of use. 

The problem we have not yet touched upon is how components can specifically move from one cellular component to another. Both the entry and the exit of SFV spike proteins are dependent on a number of such cellular processes. The newly synthesized spike proteins move from the ER to the Golgi complex and then to the cell surface. The cell surface membrane is continuously retrieved by endocytosis into endosomes. From here the endocytosed membrane components probably recycle back to the cell surface, but some components may also be channeled into lysosomes for degradation. Especially in cells with secretory activity, the recycling pathway from the cell surface also includes the Golgi complex (see Farquhar and Palade, 1981). 

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