Transport from ER Through Golgi PDF

Transport from ER Through golgi The Golgi processes proteins made by the endoplasmic reticulum (ER) before sending them out to the cell. Proteins enter the Golgi on the side facing the ER (cis side), and exit on the opposite side of the stack, facing the plasma membrane of the cell (trans side). Pro...

Transport from ER Through golgi The Golgi processes proteins made by the endoplasmic reticulum (ER) before sending them out to the cell. Proteins enter the Golgi on the side facing the ER (cis side), and exit on the opposite side of the stack, facing the plasma membrane of the cell (trans side). Proteins must make their way through the stack of intervening cisternae and along the way become modified and packaged for transport to various locations within the cell (Figure 1). The Golgi apparatus cisternae vary in number, shape, and organization in different cell types. The typical diagrammatic representation of three major cisternae (cis, medial, and trans) is actually a simplification. Sometimes additional regions are added to either side, called the cis Golgi network (CGN) and the trans Golgi network (TGN). These networks have a more variable structure, including some cisterna-like regions and some vesiculated regions. Each cisterna or region of the Golgi contains different protein modification enzymes. What do these enzymes do? The Golgi enzymes catalyze the addition or removal of sugars from cargo proteins (glycosylation), the addition of sulfate groups (sulfation), and the addition of phosphate groups (phosphorylation). Cargo proteins are modified by enzymes (called resident enzymes) located within each cisterna. The enzymes sequentially add the appropriate modifications to the cargo proteins. Some Golgi-mediated modifications act as signals to direct the proteins to their final destinations within cells, including the lysosome and the plasma membrane. What happens when there are defects in Golgi function? Defects in various aspects of Golgi function can result in congenital glycosylation disorders, some forms of muscular dystrophy, and may contribute to diabetes, cancer, and cystic fibrosis (Ungar 2009). How do cargo proteins move between the Golgi cisternae? Scientists have proposed two possible explanations: the vesicular transport model and cisternal maturation model. Interestingly, both models account for the Golgi's steady state conditions and processes, yet they do so quite differently (Figure 2). In 2002 James Rothman and Randy Schekman won the Lasker Prize for their groundbreaking work detailing the membrane and vesicle systems that make secretion possible in eukaryotic cells. These two scientists worked independently using different model organisms and different biological approaches (Strauss 2009). Together they delivered strong evidence that there are common molecules and processes involved in membrane fusion and fission in eukaryotes. Rothman and his colleagues biochemically reconstituted mammalian Golgi membranes, isolating vesicles capable of moving from one cisterna to another. As a different approach, Schekman and his colleagues used yeast genetics to identify and characterize many of the important proteins involved in secretion in this single-celled eukaryote. Over time Rothman and Schekman's work converged on several important molecules that were involved in vesicle formation and fusion, thus leading to what came to be called the vesicular transport model. Figure 2: Two models of protein trafficking through the Golgi The Vesicular Transport Model: Evidence One of the principal observations by Rothman's group was that the vesicles that formed in the Golgi moved cargo proteins between cisternae from the cis face to the trans face. These observations suported the vesicular transport model originally developed and advocated by George Palade and Marilyn Farquhar (Farquhar & Palade 1998.) The vesicular trasnport model posits that the Golgi cisternae are stable compartments that house certain protein modification enzymes that function to add or remove sugars, add sulfate groups, and perform other modifications. Vesicles arrive at each cisterna carrying cargo proteins, which are then modified by the resident enzymes located within that cisterna. Next, new vesicles carrying the cargo proteins bud from the cisterna and travel to the next stable cisterna, where the next series of enzymes further processes the protein cargo (Rothman & Wieland 1996). The Cisternal Maturation Model Before the work of Palade, Farquhar, Rothman and others who analyzed the vesicles moving proteins between Golgi cisternae, scientists thought that each Golgi cisterna was transient and that the cisternae themselves moved from the cis to the trans face of the Golgi, changing over time. The movement of proteins as passengers within cisternae through the Golgi stack is called the cisternal maturation model. This model proposes that the enzymes present in each individual cisterna change over time, while the cargo proteins remain inside the cisterna. Before Rothman's work on vesicles, this model had broad support. However, once scientists identified the large numbers of small transport vesicles surrounding the Golgi, researchers developed the vesicular transport model as an updated replacement. However, as often happens in science (and in fashion), old ideas sometimes come back in new ways Transport from golgi to outside cell This passage discusses the transport of proteins and other molecules from the trans Golgi network to the cell exterior through the process of exocytosis. It describes the constitutive and regulated secretory pathways, the formation and maturation of secretory vesicles, the localized nature of regulated exocytosis, the sorting and targeting of proteins to different plasma membrane domains in polarized cells, and the specialized synaptic vesicles found in nerve cells. Key Points Many Proteins and Lipids Seem to Be Carried Automatically from the Golgi Apparatus to the Cell Surface Proteins in the lumen of the Golgi apparatus are automatically carried by the constitutive pathway to the cell surface unless they are specifically returned to the ER, retained in the Golgi, or selected for other pathways.123 Secretory Vesicles Bud from the Trans Golgi Network 1 Secretory vesicles form from the trans Golgi network and release their contents to the cell exterior by exocytosis in response to extracellular signals.45 Secretory proteins are packaged into secretory vesicles through a mechanism involving the selective aggregation of these proteins.678 Proteins Are Often Proteolytically Processed During the Formation of Secretory Vesicles Many secretory proteins are synthesized as inactive precursors and undergo proteolytic processing during the formation and maturation of secretory vesicles.91011 This processing can produce shorter peptides that could not be transported into the ER or packaged into secretory vesicles, and it can also delay the activation of potentially harmful enzymes.121314 Secretory Vesicles Wait Near the Plasma Membrane Until Signaled to Release Their Contents Secretory vesicles travel to the site of secretion and wait at the plasma membrane until the cell receives a signal, often a chemical messenger or electrical excitation, that triggers their fusion and release of contents.15161718192021 Regulated Exocytosis Can Be a Localized Response of the Plasma Membrane and Its Underlying Cytoplasm Regulated exocytosis can be restricted to specific regions of the plasma membrane, enabling localized release of secretory products without affecting the rest of the cell.2223242526 Secretory Vesicle Membrane Components Are Quickly Removed from the Plasma Membrane After secretory vesicle fusion, their membrane components are rapidly removed from the plasma membrane by endocytosis to maintain membrane composition.2728293031323334 Polarized Cells Direct Proteins from the Trans Golgi Network to the Appropriate Domain of the Plasma Membrane Polarized cells, such as epithelial and nerve cells, have distinct plasma membrane domains to which different cargoes are selectively delivered from the trans Golgi network.353637383940 Cytoplasmic Sorting Signals Guide Membrane Proteins Selectively to the Basolateral Plasma Membrane Membrane proteins destined for the basolateral domain contain sorting signals in their cytoplasmic tails that are recognized by coat proteins for packaging into the appropriate transport vesicles.41424344 Lipid Rafts May Mediate Sorting of Glycosphingolipids and GPI-anchored Proteins to the Apical Plasma Membrane Lipid rafts that form in the trans Golgi network membrane may selectively incorporate glycosphingolipids and GPI-anchored proteins, targeting them for delivery to the apical plasma membrane domain.4546474849505152 Synaptic Vesicles Can Form Directly from Endocytic Vesicles Nerve cells have a specialized class of synaptic vesicles that store and release neurotransmitters, and these vesicles are generated locally at the nerve terminals by recycling from the plasma membrane rather than originating from the Golgi