Cellular Organelles Flashcards
Protein Trafficking
Rab-GTP and v-snare binds to vesicles
Rab effector tethering protein grabs onto Rab GTP
t-SNARE binds vesicle to membrane
v-snare and t-snare bind
vesicle fuses with target membrane and cargo is released
Rab Cycle
Responsible for getting vesicles to where they need to be
- Vesicle (with Rab-GTP and v-snare) branches off donor compartment
- Rab effector at target compartment grabs onto Rab-GTP
- t-snare brings vesicle to membrane and fuses with n-snare on vesicle
- Recycling of GTP
- GTP hydrolysis
- GDP dissociation inhibitor transports soluble Rab-GDP back to donor compartment, where guanine-nucleotide exchange factor (GEF) binds GDP and eventually phosphorylates back into GTP on new budding vesicle
Lysosome
Acidic vesicles in cytoplasm full of hydrolytic enzymes
Recycling center of cell (breaks down into small components)
Primary function: to hydrolyze all macromolecules to monomeric subunits
Substrates taken up by fusion with 1. endosomes, 2. phagosomes, 3. autophagosomes and by direct transmembrane transfer, requiring signal peptide identification
Products transported out by transporters for specific AA classes, monomeric sugars, nucleosides, FA
Hydrolases
Hydrolytic enzyme that requires acidic environment provided by H+ ATPase
Catalyzes hydrolysis of a substrate
What happens if a lysosome enzyme leaks through a pore in the membrane?
It will become inactivated because the pH in the cytosol is 7.2 and enzymes are only active in an acidic environment
Nice safeguard for the cell
Protein Trafficking to Lyso-endosome
GOLGI
- Lysosome hydrolase precursor from ER binds to mannose at cis-golgi
- Addition of P-GlcNAc
- Uncovering of M6P signal via removal of 1 GlcNAc group
- Binds to M6P receptor at trans-golgi
5. Released in vesicle headed for early endosome EARLY ENDOSOME 6. Removal of phosphate 7. Change in pH 8. Enzyme is activated as pH is dropped
- Receptors are recycled from early endosome back to trans-golgi network
Tay Sachs Disease
A lysosomal storage disease
Hexosaminidase A: Only enzyme that can hydrolyze Gm2 gangliosides in vivo
Autosomal recessive because you’d need to knock out both copies of the enzyme in order to inhibit functions
Common in inbreeding populations
Presentation: Neural, delayed milestones
See a bright red spot in patient’s eye
Mechanism: If you can’t hydrolyze the gangliosides (lipids in grey matter in brain) then they will accumulate; will send for degradation in lysosome, lysosomes grow larger bc full of ganglioside
Can accumulate in other cells, like skin or epithelial, but those cells turnover often whereas neurons do not turnover
Tay Sachs Disease
Hexosaminidase A: Only enzyme that can hydrolyze Gm2 gangliosides in vivo
Autosomal recessive because you’d need to knock out both copies of the enzyme in order to inhibit functions
Common in inbreeding populations
Presentation: Neural, delayed milestones
See a bright red spot in patient’s eye
Mechanism: If you can’t hydrolyze the gangliosides (lipids in grey matter in brain) then they will accumulate; will send for degradation in lysosome, lysosomes grow larger bc full of ganglioside
Can accumulate in other cells, like skin or epithelial, but those cells turnover often whereas neurons do not turnover
I Cell Disease (Mucolipidosis)
A lysosomal storage disease
Autosomal recessive
Defective GlcNac phosphotransferase (enzyme of Golgi that transfers phosphate to mannose residues making M6P)
Earlier presentation than Tay Sachs at 6 months. Severe cognitive delay, death by age 7.
Most severe form
All of the lipases, hydrolases, enzymes targeted to lysosomes cannot get there because you cant put the M6P tag on any of those enzymes
Blocking ability of cell to get the enzyme to the right place, meaning nothing in the lysosome will be broken down
Anterograde transport of vesicle (axonal transport)
Mediated by kinesin, which binds to vesicles and walks neuron down along the microtubule from - to +
Requires ATP
Anterograde transport of vesicle
Mediated by kinesin, which binds to vesicles and walks neuron down along the microtubule from - to +
Requires ATP
Retrograde transport of vesicle (axonal transport)
Mediated by cytoplasmic dynein, which walks recycled synaptic vesicle along microtubule from + to - back to the golgi
Stabilization of Microtubule
Has MAP2 and Tau because microtubules are unstable and can fall apart
MAP2: creates a more open conformation with distance
Tau: Creates loop, found in AD, keeps microtubule stable and in the right place
Tau Tangle Formation
- Microtubules with Tau become phosphorylated
- Aberrant phosphorylation via Pathogenic Tau kinase
- Hyperphosphorylated Tau aggregates, modifies, and undergoes conformational change
- Presence of Paired Helical Filaments (PHF)
Chronic Traumatic Encephalopathy (CTE)
Progressive degenerative disease
Common with boxing, football, ice hockey, wrestling, contact sports
Those exposed to head blasts/injuries
Head trauma > leads to accumulation of Tau protein
Symptoms: dementia (memory loss, aggression, confusion, depression)
Can appear within months of trauma or decades later
Common around blood vessels
