Golgi apparatus plasma membrane proteins

A scheme representing the possible flow of proteins along the ER —> Golgi apparatus —> plasma membrane route is shown in Figure 46—6. The horizontal arrows... 

LRRK2 protein is found in the cytosol and mitochondrial outer membrane (West et al., 2005), plasma membrane, lysosomes, endosomes, transport vesicles, Golgi apparatus, a cytoskeleton protein microtubule, synaptic vesicles, and lipid rafts (Biskup et al., 2006 Hatano et al., 2007). Interestingly, a-synuclein is also expressed in the presynaptic membranes and lipid rafts (Fortin et al., 2004). 

How is the final location of the acetylcholine receptor and secretory vesicles determined Where is the information stored to determine this localization There are two key locations in cells where sorting out of membrane proteins might occur. One of these is the Golgi apparatus and the second one involves the plasma membrane. After chromaffin granules have fused with the plasma membrane, their specific lipids and proteins are immediately and specifically removed from the latter membrane. The mechanism for this selective removal is unknown. In the Golgi apparatus, newly-synthesized membrane proteins are sorted out to various membrane vesicles. We propose a model for the sorting out of secretory vesicles from vesicles destined to deliver plasma membrane proteins. 

The membranes surrounding each cell (plasma membrane) and the intracellular structures (endoplasmatic reticulum, Golgi apparatus, nuclear membrane, mitochondria membranes, other organelle membrane) are not only composed of lipids but incorporate proteins and steroids as well. Besides this, adsorbed proteins will greatly influence the functionality of the membrane. Integral proteins can span the entire membrane. A considerable fraction of these proteins facilitates transmembrane transport of species usually not permeating the membrane. The transport mechanism may be very different. One group involves carriers... 

Endoplasmic reticulum (ER) and Golgi apparatus Inactivation of the ER-specihc enzyme acyl coenzyme A cholesterol-O-acyl transferase extensive swelling decreased synthesis and transport of plasma membrane proteins (which occurs in rough ER and Golgi apparatus)... 

Once the proteins have passed the quality control system of the early secretory pathway, they are transported in vesicles via the individual compartments of the Golgi apparatus to the plasma membrane. Soluble proteins are transported in the vesicle lumen, membrane proteins are integrated in the vesicle membrane. The transport to the cell surface is the default pathway for secretory and membrane proteins. Proteins may also become part of one of the intracellular compartments along the secretory pathway, but only if they contain specific retention signals. 

Most proteins that are synthesized on membrane-bound polyribosomes and are destined for the Golgi apparatus or plasma membrane reach these sites inside transport vesicles. The precise mechanisms by which proteins synthesized in the rough ER are inserted into these vesicles are not known. Those involved in transport from the ER to the Golgi apparatus and vice versa—and from the Golgi to the plasma membrane— are mainly clathrin-free, unlike the coated vesicles involved in endocytosis (see discussions of the LDL receptor in Chapters 25 and 26). For the sake of clarity, the non-clathrin-coated vesicles will be referred to in... 

Many proteins synthesized on membrane-bound polyribosomes proceed to the Golgi apparatus and the plasma membrane in transport vesicles. 

Like other cells, a neuron has a nucleus with genetic DNA, although nerve cells cannot divide (replicate) after maturity, and a prominent nucleolus for ribosome synthesis. There are also mitochondria for energy supply as well as a smooth and a rough endoplasmic reticulum for lipid and protein synthesis, and a Golgi apparatus. These are all in a fluid cytosol (cytoplasm), containing enzymes for cell metabolism and NT synthesis and which is surrounded by a phospholipid plasma membrane, impermeable to ions and water-soluble substances. In order to cross the membrane, substances either have to be very lipid soluble or transported by special carrier proteins. It is also the site for NT receptors and the various ion channels important in the control of neuronal excitability. 

Figure 12.2 Copper chaperone function, (a) Copper homeostasis in Enterococcus hirae is affected by the proteins encoded by the cop operon. CopA, Cu1+-import ATPase CopB, Cu1+-export ATPase CopY, Cu1+-responsive repressor copZ, chaperone for Cu1+ delivery to CopY. (b) The CTR family of proteins transports copper into yeast cells. Atxlp delivers copper to the CPx-type ATPases located in the post Golgi apparatus for the maturation of Fet3p. (c) Coxl7p delivers copper to the mitochondrial intermembrane space for incorporation into cytochrome c oxidase (CCO). (d) hCTR, a human homologue of CTR, mediates copper-ion uptake into human cells. CCS delivers copper to cytoplasmic Cu/Zn superoxide dismutase (SOD1). Abbreviations IMM, inner mitochondrial membrane OMM, outer mitochondrial membrane PM, plasma membrane PGV, post Golgi vessel. Reprinted from Harrison et al., 2000. Copyright (2000), with permission from Elsevier Science.

Clathrin-coated vesicles mediate transport from the Golgi apparatus to endosomes, and from the plasma membrane to endosomes. A multi-subunit protein, clath-rin, constitutes the major protein of this vesicle type (see Ch. 2). Clathrin is composed of three large and three small polypeptide chains, which assemble to form a triskelion (Fig. 9-2). Regulatory mechanisms control the assembly and formation of a convex, polyhexa-pentagonal basketlike structure by these triskelions [5], This structure is responsible for the formation of coated pits on the cytosolic face of plasma membranes. 

As noted above, synaptic vesicles are not typically generated at the level of the TGN. Instead, they are assembled from endocytosed material retrieved from the synaptic plasma membrane. Synaptic vesicle and plasma membrane lipids and proteins are synthesized in the endoplasmic reticulum and modified in the Golgi apparatus, where they are then packaged in secretory vesicles. These synaptic precursors are delivered to the plasma membrane from the cell body by the constitutive secretory pathway. Synaptic vesicle proteins must be retrieved by clathrin-mediated synaptic vesicle endocytosis, a variant of RME with some neuron-specific components. Once the vesicle sheds its clathrin coat, the uncoated vesicle fuses with a... 

In spite of the variety of appearances of eukaryotic cells, their intracellular structures are essentially the same. Because of their extensive internal membrane structure, however, the problem of precise protein sorting for eukaryotic cells becomes much more difficult than that for bacteria. Figure 4 schematically illustrates this situation. There are various membrane-bound compartments within the cell. Such compartments are called organelles. Besides the plasma membrane, a typical animal cell has the nucleus, the mitochondrion (which has two membranes see Fig. 6), the peroxisome, the ER, the Golgi apparatus, the lysosome, and the endosome, among others. As for the Golgi apparatus, there are more precise distinctions between the cis, medial, and trans cisternae, and the TGN trans Golgi network) (see Fig. 8). In typical plant cells, the chloroplast (which has three membranes see Fig. 7) and the cell wall are added, and the lysosome is replaced with the vacuole. 

In a simplified view, the total flow is as follows (Fig. 8). Both soluble and membrane proteins that are translated at the membrane-bound ribosome are first localized at the ER. Some of them are transported to the Golgi apparatus, whereas others remain at the ER. At the Golgi apparatus, including the trans Golgi network (TGN), the next selection occurs some are transported to the plasma membrane, others to the endosome and to the lysosome/vacuole finally, and still others remain there. The lysosome is also an important organelle for the other transport system, the endocytic pathway. In this pathway, proteins at the plasma membrane are internalized by endocytosis. The sorting to lysosomes is treated in the next section. 

Proteins can undergo different rounds of palmitoylation and depalmitoylation, either constitutively or as a response to signals." " Here the Ras proteins are the most commonly discussed examples. As described above, all Ras proteins are expressed with the CAAX-box and are subject to post-translational modifications. First, they get farnesylated and after proteolysis and methylation of the C-terminus, H-/N-Ras as well as K-Ras 4A get further palmitoylated at additional cysteines present in their C-terminus. Palmitoylation occurs in the Golgi apparatus and via vesicular transport the farnesylated and palmitoylated proteins are directed to the plasma membrane (PM). The palmitoyl thioester is hydrolyzed at multiple cellular sites and the protein is transported back to the Golgi via a nonvesicular pathway (Scheme 3)." ... 

---