Sorting signals and cellular membranes

G Warren
1987 BMJ (Clinical Research Edition)  
Cells use a surface receptor protein to trap and internalise the cholesterol they need for membrane synthesis. The receptor protein is synthesised on ribosomes, which become bound to the membrane of the endoplasmic reticulum (fig 1) . The receptor protein is then transported via vesicles through the Golgi stack, where it undergoes a variety ofmodifications before appearing on the cell surface. Here the receptor protein binds circulating low density lipoprotein, a cholesterol carrier, and the
more » ... are internalised by surface invaginations called coated pits. These pinch off to form coated vesicles, and uncoating is followed by fusion with endosomes. Low density lipoprotein is parted from the receptor, delivered to lysosomes, and degraded; the cholesterol so released passes to the endoplasmic reticulum, where membrane synthesis takes place. The receptor is recycled from the endosomes back to the cell surface, where it participates in roughly a hundred more rounds of internalisation. It too is then degraded in lysosomes. Cellular compartments The life cycle of the low density lipoprotein receptor is characterised by movement from one membrane bound compartment to the next in a highly ordered and efficient manner. Compartmentation is a major feature distinguishing eukaryotes from prokaryotes and enables them to carry out many different cellular functions under optimal conditions. Since the focus of this review is proteins I shall define a compartment as a collection of soluble proteins surrounded by a membrane. Different compartments have different collections of soluble and membrane proteins, though some proteins may be common to both compartments. The function of the endosome, for example, is to separate complexes such as low density lipoprotein from their receptor. Binding of the two is sensitive to acid so the membrane of the endosome contains proton pumps which keep the inside acidic, causing the low density lipoprotein to dissociate from the receptor. The lysosome also has proton pumps in the membrane to keep the inside acidic, but this is to allow the soluble degradative enzymes that it contains to work optimally. One might ask why there is a need for both endosomes and lysosomes. Since lysosomes are acidic low density-lipoprotein could be both released from the receptor and then degraded. The answer is that the receptor would also be degraded. The endosome serves to protect the receptor for further rounds of internalisation. The sorting problem What is true for endosomes and lysosomes is also true for all other cellular compartments. They have each evolved to carry out a 1.ted FIG I-Synthesis and cycling of the low density lipoprotein receptor. Messenger ribonucleic acid (mRNA) coding for the receptor leaves the nucleus and is translated on ribosomes, which become attached to membrane of the endoplasmic reticulum. After transport to the cell surface the receptor binds low density lipoprotein (LDL) and delivers it to the endosomes, recycling back to the cell surface to bind more low density lipoprotein. Degradation of low density lipoprotein in lysosomes releases the cholesterol needed for membrane synthesis. particular set of functions which confer unique advantages on the eukaryotic cell. These specialisations, however, create a major problem, which is the focus of this review. The problem is in two parts, the first concerning the growth and division of eukaryotic cells. These must be accompanied by the growth and division of the membrane bound compartments, which in turn necessitates the synthesis of the membrane and soluble proteins that make up each compartment. The largest compartment in the cell, the cytoplasm (bounded by the plasma membrane), is specialised for protein synthesis probably because most of the proteins synthesised in the
doi:10.1136/bmj.295.6608.1259 fatcat:ib3q5ncvcbb7hjxhsdfiffhi7m