Ridge February 12, 2016, 01:42 PM BaConCell Lecture Notes Page 1 The endomembrane system, part 1. (compartments; protein sorting) Alberts et al. read Chapters 12 and 13 1. All eucaryotic cells have the same basic set of membrane-bounded organelles, and many vital biochemical processes take place in or on membrane surfaces (such as we have seen with mitochondria and chloroplasts). 2. The major intracellular compartments common to all cells are: the cytoplasm itself (consisting of the organelles and the cytosol) the nucleus, the endoplasmic chloroplasts (in reticulum, plants), the Golgi lysosomes, apparatus, mitochondria, endosomes, peroxisomes (microbodies). The relative volumes of these organelles can vary but an example is given in Table 12-1 for the hepatocyte, and a comparison for relative amounts of membrane types in hepatocytes and exocrine cells are compared in Table 12-2. 3. The organelles are not randomly distributed in the cell but are positioned according to function and the special purpose of the cell itself. For example, the Golgi apparatus is usually found close to the nucleus, whereas the ER extends from the nucleus far out into the cytosol. Organelle positioning is highly dependent on the cytoskeleton, and disruption of the cytoskeleton leads to breakdown of the internal organisation of the organelles. How proteins move between compartments. 4. Proteins are synthesized on ribosomes in the cytosol (a few are also made in mitochondria and chloroplasts). The subsequent fate of the protein depends on their amino acid sequence, in particular the presence of specific sequences of amino acids called sorting signals. Proteins that do not have signal regions remain in the cytosol. 5. To understand how sorting signals work, we must consider first how proteins can move from one compartment to another. This movement can Ridge February 12, 2016, 01:42 PM BaConCell Lecture Notes Page 2 be between compartments of topological equivalence or difference. See Figure 12-7. 6. Between the nucleus and cytosol, proteins move through the nuclear pore complexes, in a process called gated transport, where the complexes function as selective gates. Because of the nuclear pore, the nucleus is considered to be topologically equivalent to the cytosol. 7. In movement through membranes (trans-membrane transport) special protein translocators directly transport proteins through the membrane from the cytosol to a topologically different compartment. The transported protein must unfold to snake through the membrane. 8. In vesicular transport, transport-vesicles ferry proteins from compartment to another, such as between the ER and Golgi. one Because vesicles pinch off one compartment and fuse with another, then the contents are considered to be topologically equivalent. 9. Sorting signals come in two basic flavours (see Figure 12-8 and Table 123). Signal peptides usually come at the end of the amino acid sequence as a special set of amino acids, although they can be located elsewhere. Signal patches are sequences located at different places on the protein that can come together when the final conformation of the protein is made. 10. Most proteins destined for the ER, mitochondria, chloroplasts, peroxisomes, and nucleus are the signal peptide type. Much less is known about signal patches, although there is some evidence that signal patches are used to direct traffic from Golgi to lysosomes. 11. Proteins that enter the ER, for example, will not leave that compartment again, and often the signal peptide is cleaved by a signal peptidase. However, proteins that enter the nucleus are often transported out again, and they retain their signal sequence. Perhaps this is why nuclear signal sequences are not at the end of the protein but within it.