Lysosomal integral membrane proteins

In the very rare and fatal Niemann-Pick Cl disease lysosomes in cells of the central nervous system and the viscera accumulate LDL-derived cholesterol. Study of the DNA of patients led to discovery of a 1278-residue integral membrane protein, which may be required for the Golgi-mediated transport of unest-erified cholesterol from lysosomes to the ER.189/232 234c... 

Fig. 6.2. Model for how FcRn rescues IgG from catabolism by recycling and transcytosis. IgG and many other soluble proteins are present in extracellular fluids. Vascular endothelial cells are active in fluid phase endocytosis of blood proteins. Material taken up by these cells enters the endosomes where FcRn is found as an integral membrane protein. The IgG then binds FcRn in this acidic environment. This binding results in transport of the IgG to the apical plasma membrane for recycling into the circulation, or to the basolateral membrane for transcytosis into the extracellular space. Exposure to a neutral pFI in both locations then results in the release of IgG. The remaining soluble proteins are channeled to the lysosomal degradation pathway.

In eukaryotic cells, a ribosome remains free in the cytoplasm unless it is directed to the endoplasmic reticulum (ER), the extensive membrane system that comprises about half the total membrane of a cell. The region that binds ribosomes is called the rough ER because of its studded appearance, in contra.sl with the smooth ER, which is devoid of ribosomes (Figure 30.28). Free ribosomes synthesize proteins that remain within the cell, either within the cytoplasm or directed to organelles bounded by a double membrane, such as the nucleus, mitochondria and chloroplasts. Ribosomes bound to the ER usually synthesize proteins destined to leave the cell or to at least contact the cell exterior from a position in the cell membrane. These proteins fall into three major classes secretory proteins (proteins exported by the cell), lysosomal proteins, and proteins spanning the plasma membrane. Virtually all integral membrane proteins of the cell, except those located in the membranes of mitochondria and chloroplasts, are formed by ribosomes bound to the ER. 

Synthesis of secreted proteins enzymes destined for the ER, Golgi complex, or lysosome and Integral plasma-membrane proteins begins on cytosolic ribosomes, which become attached to the membrane of the ER, forming the rough ER (see Figure 16-1, left). 

Cellular location of ribosomes In eukaryotic cells, the ribosomes are either "free" in the cytosol or are in close association with the endoplasmic reticulum (which is then known as the "rough" ER or RER). The RER-associated ribosomes are responsible for synthesizing proteins that are to be exported from the cell, as well as those that are destined to become integrated into plasma, ER, or Golgi membranes, or incorporated into lysosomes (see p. 167 loan overview of the latter process). [Note Mitochondria contain their own set of ribosomes and their own unique, circular DNA.]... 

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