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Chapter 13 Intracellular Vesicular Traffic
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Vesicular transport
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The endocytic and biosynthetic-secretory pathways
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The three well-characterized types of coated vesicles differ in their
coat proteins
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Utilization of different coats in vesicular traffic
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Assembly of a clathrin coat drives vesicle formation
Clathrin-coated pits and vesicles
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The structure of a clathrin coat
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The assembly and disassembly of a clathrin coat
The pinching-off and uncoating of coated vesicles are regulated processes The assembly and disassembly of a clathrin coat
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Not all coats form basketlike structures
A model for retromer assembly on endosomal membranes
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Phosphoinositides mark organelles and membrane domains
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The intracellular location of phosphoinositides
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leaflets of the lipid bilayers flow together
The role of dynamin in pinching off clathrin-coated vesicles from the membrane Dynamin together with other proteins destabilize the membrane so that the noncytoplasmic leaflets of the lipid bilayers flow together
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The coats of COPI and COPII vesicles consists of large
protein complexes that are composed of - seven individual coat-protein subunits for COPI coats, and - four individual coat-protein subunits for COPII coats Some COPI coat-protein subunits show sequence similarity to adaptins
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Vesicular transport does not necessarily occur only through
uniformly sized spherical vesicles, but can involve larger portions of a donor compartment
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Monomeric GTPases control coat assembly
Assembly of a COPII-coated vesicle
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Rab proteins guide vesicle targeting
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SNARE proteins and targeting GTPases guide membrane transport
SNAREs contribute to the selectivity of transport-vesicle docking and fusion, while the GTPases (Rabs) regulate the initial docking and tethering of the vesicle to the target membrane
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The formation of a Rab5 domain on the endosome membrane
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SNAREs mediate membrane fusion
Structure of a trans-SNARE complex
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A model for how SNARE proteins may ccatalyze membrane fusion
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Interacting SNAREs need to be pried apart before they can function again
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Viral fusion proteins and SNAREs may use similar fusion mechanisms
The entry of enveloped viruses into cells
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Proteins leave the ER in COPII-coated transport vesicles
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Only proteins that are properly folded and assembled can leave the ER
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Homotypic membrane fusion
Transport from the ER to the Golgi apparatus is mediated by vesicular tubular clusters Homotypic membrane fusion
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Vesicular tubular clusters move along the microtubules to carry
proteins from the ER to the Golgi apparatus
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The retrieval pathway to the ER uses sorting signals
The best-characterized signal for ER membrane proteins is KKXX present at the C-terminus and this signal interacts directly with the COPI coat . Soluble ER resident proteins contain the signal sequence KDEL at their C-terminus and this signal interacts with the KDEL receptor, a multipass transmembrane protein.
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cluster and the Golgi apparatus
The pH-dependent retrieval of ER resident proteins from the vesicular tubular cluster and the Golgi apparatus Many proteins are retained in the ER as a result of kin recognition
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The length of the transmembrane region of Golgi enzymes
determines their location in the cell
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The Golgi apparatus consists of an ordered series of compartments
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Molecular compartmentalization of the Golgi apparatus
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Oligosaccharide chains are processed in the Golgi apparatus
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The two main classes of N-linked oligosaccharides found in mature mammalian glycoproteins
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Oligosaccharide processing in the ER and the Golgi apparatus
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Proteoglycans are assembled in the Golgi apparatus
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Two possible models for transport of proteins through the Golgi apparatus
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Lysosomes are the principal sites of intracellular digestion
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A model for lysososme maturation
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Multiple pathways deliver materials to lysosomes
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A mannose 6-phosphate receptor recognizes lysosomal proteins in the
trans Golgi network
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The M6P receptor shuttles between specific membranes
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A signal patch in the hydrolase provides the cue for M6P addition
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Endocytosis Two main types of endocytosis distinguished on the basis of the size of the endocytic vesicle formed. Phagocytosis involves ingestion of large particles and is a triggered process. Pinocytosis involves ingestion of fluid and solutes via small pinocytic vesicles and is a constitutive process that occurs continuously
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Specialized phagocytic cells can ingest large particles
A macrophage ingesting red blood cells
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Phagocytosis by a neutrophil
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Pinocytic vesicles form from coated pits in the plasma membrane
Formation of clathrin-coated vesicles from the plasma membrane
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Not all pinocytic vesicles are clathrin-coated
Caveolae in the plasma membrane of a fibroblast
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Cells import selected extracellular macromolecules by receptor-mediated endocytosis
Most cholesterol is transported in the blood as low-density lipoprotein (LDL) particles
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Normal and mutant LDL receptors
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The receptor-mediated endocytosis of LDL
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Possible fates for transmembrane receptor proteins that have been endocytosed
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Exocytosis
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Constitutive secretory pathway – all cells
Regulated secretory pathway – found mainly in specialized cells
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The three best-understood pathways of protein sorting in the trans Golgi network
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Secretory vesicles bud from the trans Golgi network
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Exocytosis of secretory vesicles
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Proteins are often proteolytically processed during the formation of
secretory vesicles Alternative processing pathways for the prohormone proopiomelanocortin
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Polarized cells
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Sorting of plasma membrane proteins in a polarized epithelial cell
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Most synaptic vesicles are generated by local recycling from the plasma membrane
in the nerve terminals
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A model of a synaptic vesicle
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