ch 8 pt3

• Cis golgi network: sorts proteins for the ER or the next golgi station
• The medial cisternae is where processing takes place at the golgi complex
• The trans golgi network functions in sorting proteins either to the membrane or various intracellular destinations
• The N-linked oligosaccharide that was added to proteins in the ER is further processed in the golgi apparatus
• O-linked glycoproteins are attached to a serine or threonine hydroxyl, unlike n-linked glycoproteins whose oligosaccharides are attached to the amide group of asparagine
• Glycosylation of proteins makes them chemically distinct
• In the vesicular transport model, anterograde cargo is shuttled from the CGN to the TGN in vesicles
• In the cisternal maturation model, each cistern "matures" as it moves from the cis face to the trans face
• In both the vesicular transport model and the cisternal maturation model, there is retrograde transport of vesicles
• The vesicular tubular cluster (VTC) is located in the endoplasmic reticulum-golgi intermediate compartment (ERGIC) is an organelle involved in mediating traffic between the ER and golgi
• COPII-coated vesicles move materials from the ER to the VTC/ERGIC and golgi complex

  
• COPI-coated vesicles move materials from the VTC/ERGIC and golgi backwards, from the trans golgi to the cis golgi cisternae
• COPII-coated vesicles are antegrade transporters
• COPI-coated vesicles are retrograde transporters
• Clathrin coated vesicles move materials from the TGN to endosomes and lysosomes

  
• Most soluble resident ER proteins carry a KDEL sequence in their C-terminus that binds to a KDEL receptor at the cis-golgi network which returns the protein to the ER
• Retrograde transport of KDEL proteins is faciliatated by COPI
• Vesicle budding begins with the recruitment of a small GTP-binding protein to the donor membrane followed by binding of the cytosolic coat proteins to the cystolic domain of membrane cargo proteins
• T-snares on the target membrane bind to the V-snare of the vesicle membrane, initiating fusion
• Clatherin coats are involved in trans-golgi network to endosomes and plasma membranes to endosomes
• Clatherin: major protein component of clatherin coated vesicles
• Triskelion: clatherin molecule consisting of three large and three small polypeptide chains
• There are 36 triskelions per clatherin coat
• Lysosomes contain hydrolytic enzymes produced in the RER which can hydrolyze virtually any type of biological macromolecule
• Lysosomal enzymes optimally operate in an acidic lumen where pH=4.6 that is maintained by a proton pump
• Lysosomal membranes have highly glycosylated integral proteins that form a barrier against the enclosed enzymes
• Clathrin-coated vesicles are used to sort and transport lysosomal enzymes
• Lysosomal proteins are tagged in the cis-golgi complex with phosphorylated mannose residues, which are then captured and recognized by mannose 6-phosphate receptors (MPR), bound by coat proteins
• Mannose 6 phosphate residues are added in the cis-golgi, then binds to a mannose 6 phosphate receptor in the trans-golgi
• Clathrin-coated vesicles that transport lysosomal enzymes consist of

  • outer lattice composed of clathrin
  • inner cell of GGA adaptor proteins
  • g-proten arf1-gtp used for membrane curvature and recruiting adaptors
• Early endosomes are generated by receptor mediated endocytosis and fuse with late endosomes
• Late endosomes either transition to lysosomes or fuse with existing lysosomes
• Autophagy: utilization of lysosomes to degrade cytosolic proteins and organelles
• Phagophore: double membrane structure that envelopes an organelle to produce an autophagosome that degrades its enclosed contents
• Targeting vesicles to a particular compart

  1. movement of the vesicle towards their target compartment by microtubules and motor proteins
  2. tethering vesicles to the target compartment, by tethering proteins
  3. docking vesicles to the target compartment via integral proteins
  4. fusion between vesicle and target membrane
• Exocytosis: discharge of a secretory vesicle or granule after fusion with plasma membrane initiated by an increase in calcium
• Fusion pore: vesicle and plasma membrane merging together
• The luminal part of the vesicle membrane becomes the outer surface of the plasma membrane, while the cytosolic part becomes the inner surface of the PM
• There are two types of endocytosis: bulk-phase endocytosis and receptor-mediated endocytosis
• Bulk-phase endocytosis/pinocytosis is the nonspecific uptake of extracellular fluids and functions to recycle membrane between the cell surface and interior compartments