BIOMG 1350 1st Edition Lecture 12 Outline of Last Lecture I. Secretory PathwayOutline of Current Lecture II. Retrieval PathwayIII.Endocytosis:IV. ClathrinV.Current Lecture- Retrieval Pathway:o Backwards pathway regulated by COP I:  How it works: Discovered by examining what would happen if lumen proteins escaped to the cis Golgi Soluble ER proteins contain the KDEL recognition signal, and bind the KDEL Receptor for transport back to the ER by COPI coat vesicles Environmental condition in ER do not favor KDEL- receptor relationship in ER Active VSNARE: transmembrane protein fuses with TSNARE on Golgi ER proteins is depleted  VSNARE gets inactivated in retrieval pathway in order to get brought back. Otherwise all of the VSNARE would stay in the Golgi. It therefore directs traffic from ER to Golgi.- Coat protein going back to ER still have an active retrieval VSNARE inactivated when going in forward direction- Endocytosis:o The taking in of material by the invagination of plasma membraneo Receptor mediated: Cholesterol in the blood is carried by the LDL particle. Problem: too much LDL causes atherosclerosis High LDL can be caused by genetic diseases such as FH FH due to the inability to take up LDL from the blood These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute. The LDL receptor on the cell surface binds LDL and internalizes it through clathrin coated pits - The founders found that LDL has a very high affinity receptor in unaffected cells- In mutants, they have defective receptors that cant bind to LDL- Other patients had cell surface receptor that bound LDL, yet could not bind. Mutations were on the cytosolic [art of the receptor. - Localization of the receptor coated pits must be necessary for the uptake of LDL  cytosolic side matters- Called Receptor Mediated Endocytosis- Receptor will only leave endosomes when it releases LDL- LDL particles taken to lysosomes and free cholesterol is released Exploited by many viruses to gain entry into a cell. Once it is in the early endosome, the low pH allows it to escape and be free in the cell- Example: flu virus- Clathrin:o Adaptin-2 and cargo receptors select molecules for transporto Cargo, cargo receptors, adaptin, clathrin- Lysosomes and their Biogenesis:o Lysosomes: Acidic organelles (pH 5) Protein Pumps Acid Hydrolases Membrane transporters so products of degradation can be reused  Membrane proteins lining the lumen are glycosylated to protect them from the harsh environment Partially denatured at pH 5.0 so it results in rapid substrate degradationo Delivery of lysosomal enzymes by recycling the Lysosomal Enzyme Receptoro It then goes to early endosome in endosome lysosome dissociates form clathrin clathrin recycled by back Golgio If the acid pH in the early endosome was neutralized: LDL would stop being takenup because LDL receptors would all get stuck in the early endosome and lysosomal enzymes would be secreted stillo Different receptors= different pathways- Phagocytosis:o Involves the uptake of large molecules, encloses in plasma membrane and engulfed, transport and fusion with a lysosome where the lysosomal enzyme will break down the particleo Part of immune systemo Asbestosis: can’t be broken down in lysosomes, causes lysosomes to rupture and release lysosomal enzymes into the cytosol (which is very deleterious to the