- TGN (trans Golgi network) sorts proteins going out to lysosome, exterior, etc.
- lysosome: membrane-bound organelle with hydrolytic enzymes inside
- e.g. proteases, lipases, phosphatases, nucleases, etc.
- acid hydrolase: general term for all of those enzymes, are activated by proteolytic cleavage and acid environment (pH 4.5 - 5.0)
- lysosomal membranes are glycosylated to prevent the organelle from digesting itself (sugar addition blocks cleaving)
- the end products of digestion get sent back to cytosol for reuse
- vacuolar H+ ATPase: a pump in the lysosome membrane, pumps in H+ to keep acid and build concentration gradient, as H+ goes out, small subunits also go out (remember symport?)
- lysosomes are diverse in shape and size but are biochemically identical (a certain Ab stains only organelles with hydrolases, and the images showed that these large or small, round or elliptical bodies were in fact all lysosomes)
- diverse in function: lysosomes digest intra/extracellular debris, make nutrients, and destroy phagocytosed microbes
- diverse in formation: lysosomes progress through different stages from endosome (initial formation of membrane vesicle plus new enzymes plus new food) to endolysosome (fuse with existing lysosome for extra materials) to mature lysosome (most of the new food is all digested)
- vacuoles: very large fluid-filled vesicles in plant/fungi
- store nutrients, degrade waste, cheap volume growth, maintain turgor pressure, maintain chemical homeostasis (store excess chemicals in the vacuole so cytosol concentrations are constant)
- endocytosed molecules first enter the cell in a pinched off vesicle
- vesicle meetes early endosome and fuses
- some stuff (either membrane or content) gets sent back to the plasma membrane
- pump is slowly building up acidity of endosome, becomes late endosome
- either meets a lysosome to form an endolysosome or digests all by itself and mature into a lysosome directly
- bud off endosome membrane to give back to Golgi
- autophagy: self-degradation of organelles
- retiring organelle gets wrapped up in another membrane to form an autophagosome and fuses with a lysosome
- in starving conditions, cell digests some cytosol too
- also helps in restricting development
- enclosed tubular membrane must envelope and then reseal around organelle
- phagocytosis is a similar process
- how do lysosomal proteins reach the lysosome?
- both lysosomal hydrolases and lysosomal membrane proteins get transported into rough ER and then to TGN
- transport vesicles bud from TGN, only lysosomal proteins are brought
- Mannose-6-Phosphate (M6P) receptor: transmembrane receptor in TGN, recognizes the M6P groups added onto only the N-linked oligosaccharides of the lysosomal proteins
- this is delivered to early endosomes
- receptor binds at pH 6.5 - 6.7 and releases at pH 6 (late endosomes)
- an acid phosphatase in the endosome removes the phosphate from the mannose, so the signal is gone
- retromer complex: coat protein that recognizes the cytoplasmic tails of the M6P receptor to form a vesicle
- retromer-coated vesicles return M6P receptors to the Golgi
- some lysosomal proteins may escape receptor binding and end up outside the cell, but they do no harm (ECM pH is 7.4)
- lysosomal proteins have signal patch to receive M6P
- GlcNac phosphotransferase in cis Golgi binds at signal patch and adds GlcNac-phosphate to one or two of the mannose res on each oligosaccharide chain
- second enzyme in trans Golgi cleaves off GlcNac to leave behind the phosphate on the mannose
- since each protein has many oligosaccharide chains, they consequently have many M6P, making the binding to the receptor high affinity (more to love :D)
pg. 779 - 785 (from Chapter 13)
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