Class 13 - Lysosomes and Proteasome (GOOD) Flashcards
M6P
Marker which allows recognition and selection of lysosomal hydrolases to be transported to lysosomes
Signal added in cis Golgi network to N-linked oligosaccharides.
M6P receptor protein
Transmembrane protein found in the TGN which recognize M6P groups, bind to lysosomal hydrolases, and bind to adaptor proteins assembling clathrin coats.
Uses signals at cytoplasmic tail to guide direction and allow recognition at TGN or endosome.
Binds at high pH and releases at low pH of endosome lumen
Lysosomal storage diseases
Genetic defects that affect one or more lysosomal hydrolase (e.g. Hurler’s disease) which are excreted because of mis-sorting.
Result in accumulation of undigested substrates in lysosomes. Typically affect nervous system.
In worst form (I-cell disease) lysosomes don’t receive M6P tags —> inclusions form in the cell, impacting organs, skeleton, and mental development.
Lysosome
Membrane enclosed, highly glycosylated membrane proteins. All eukaryotic cell.
Hydrolytic enzymes for digesting
macromolecules. Site for degradation and recycling of proteins, nucleic acids, and lipids (autophagy).
Has H+ pumping into it to keep pH low, also providing H+ gradient across membrane.
Final products put in cytosol and reused or excreted.
Heterogenous - Morphologically diverse
Acid hydrolase
Hydrolytic enzymes in lysosomes which break down molecules.
pH in lysosome kept low (acidic) so acid hydrolase can function.
Vacuole
Large fluid filled vesicles found in plants and fungi (equivalent to animal cell lysosome).
Store nutrients and waste, degradation, increase cell size, control turgor pressure (help balance pH).
Autophagy
4th pathway - “Self-eating.” Used to digest cytosol, worn-out organelles, and microbes that invade the cytosol.
Cytoplasm portion engulfed into membraned autophagosome which fuses with a lysosome to be degraded.
Roles: Helps restructure differentiating cells by removing unwanted cellular contents, recycle existing molecules, degrade bacteria/viruses and damaged molecules.
Autophagosome
Membrane structure during autophagy which engulfs a portion of the cytosol then fuses with a lysosome to be degraded.
Nonselective autophagy
Bulk portion of cytoplasm sequestered into autophagosomes. Does not require ubiquitin tag.
Selective autophagy
Autoohagosomes tightly enclose specific cargo and mostly exclude surrounding cytosol. Requires ubiquitin tag.
Proteasome
Abundant proteins dispersed throughout cytosol and nucleus (if protein is in ER, it’s translocated to cytosol).
Central hollow cylinder with protein subunits. Proteins threaded through using ATP and exposed to proteases lining proteasome core.
Ubiquitin
Act as a mark for cargo destined for degradation via selective autophagy.
Attached as a polyubiquitin chain on misfolded proteins. Delivers proteasome.
Default pathway
To the cell surface.
Also called the nonselective constitutive secretory pathways.
Macropinocytosis
2nd pathway - Nonspecific uptake of fluids, membranes, and particles attached to plasma membrane.
Phagocytosis
3rd pathway - Found in phagocytic cells and involved engulfment (phagocytosis) of large particles and microorganisms to form phagosomes.