Term
| Step 1. of Secretory and Endocytic Pathways |
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Definition
Co-Translational insertion of proteins into the ER membrane or lumen
- protein folding
- protein modification
- N-linked glycosylation
- O-linked glycosylation
- disulfide bonding |
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Term
| Step 2. of Secretory and Endocytic Pathways |
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Definition
In the ER, cargo proteins are packaged into ANTEROGRADE vesicles
- released anterograde vesicles then fuse to form the cis-Golgi network |
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Term
| Step 3. of Secretory and Endocytic Pathways |
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Definition
ER-specific proteins are retrieved in RETROGRADE vesicles
- ER proteins have an ER retention signal |
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Term
| Step 4. of Secretory and Endocytic Pathways |
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Definition
Cisternal Maturation
- proteins undergo further modification (carbohydrate modifications)
- layers move from cis- to medial- to trans- |
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Term
| Step 5. of Secretory and Endocytic Pathways |
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Definition
Retrograde transport
- enzymes are shuttled back to their appropriate site of function |
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Term
| Step 6. of Secretory and Endocytic Pathways |
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Definition
Trans-Golgi network
- proteins are sorted for targeted delivery
- constituitive exocytosis |
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Term
| Step 7. of Secretory and Endocytic Pathways |
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Definition
Trans-Golgi network
- proteins are sorted for targeted delivery
- regulated exocytosis |
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Term
| Step 8. of Secretory and Endocytic Pathways |
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Definition
Trans-Golgi network
- proteins are sorted for targeted delivery
- lysosomal delivery
- occurs vis the late endosome |
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Term
| Step 9. of Secretory and Endocytic Pathways |
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Definition
Endocytosis
- proteins are sorted for targeted deliver
- fates of endosomal proteins
- recycled to the membrane: various receptors
- lysosomal delivery: various receptor ligands, occurs via the late endosome |
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Term
| Common themes in Vesicle Budding |
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Definition
1. Small GTPase is recruited to the parent membrane
2. Coat proteins recognize specific small GTPases
3. Coat proteins gather appropriate cargo
4. Coat proteins gather appropriate v-SNARES
5. Coat proteins polymerize to induce membrane curvature
6. Completed vesicle detach
7. Coat proteins shed from detached vesicles |
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Term
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Definition
COP I
COP II
Clathrin/Adapter Protein |
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Term
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Definition
cis-Golgi --> ER
medial-Golgi --> cis-Golgi
trans-Golgi --> medial-Golgi
TGN --> trans-Golgi
- ARF (small GTPase)
- retrograde transport: recovery of v-SNARE proteins, membrane retrieval, missorted ER proteins (KDEL C-terminal motif) |
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Term
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Definition
ER --> cis-Golgi (anterograde transport)
- Sar1 (small GTPase) |
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Term
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Definition
trans-Golgi --> endosomes
plasma membrane --> endosomes
- ARF (small GTPase) |
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Term
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Definition
- integral membrane protein in the ER membrane
- Sar1 GEF protein |
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Term
| Sar1 regulation of COP II Vesicle Coating |
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Definition
- Sec12 catalyzes GTP exchange on Sar1
- GTP binding "unfolds" hydrophobic N-terminus
- N-terminus "anchors" acting GTP-Sar1 to the ER membrane
- GTP-Sar1 binds COPII coat proteins
- specific membrane "cargo" proteins bind coat protein complexes
- following vesicle detachment: specific coat proteins have GAP activity (GTP-Sar1 is hydrolzyed to GDP-Sar1)
- GDP-Sar1 releases coat proteins
- GDP-Sar1 releases from the vesicle membrane |
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Term
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Definition
blocks decoating of COPII vesicles
- non-hydrolyzable GTP analog |
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Term
| Vesicle Docking to Target Membranes |
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Definition
Directed by Rab GTPases
- part of the ras superfamily of small GTPases
- isoprenylated on their N-terminus
- integrate with specific transport vesicles
- Rab effector proteins direct docking of GTP-Rab vesicles
- there are ~ 70 distinct Rab proteins
- each 'donor' vesicle type has a distinct Rab protein
- each 'recipient' membrane has a distinct Rab effector protein
- v-SNARES: vesicle membrane, t-SNARES: target menbrane
- binding forms coiled tetramers
- 'coiling' brings membranes into close apposition, membranes fuse |
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Term
| NSF (N-ethylmaleimide Sensitive Factor) and a-SNAP |
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Definition
required to dissociate v-/t-SNARE complexes
- requires ATP hydrolysis
- freed SNARES again available for more vesicle docking/fusion |
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Term
| Post-trans-Golgi delivery sites |
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Definition
1. Retrograde trans-Golgi
- coat = COPI
2. Direct Lysosome delivery
- coat = AP3
- coat = Clathrin???
3. Late Endosome/Lysosome
- coat = Clathrin/AP1
4. Constituitive PM delivery
- coat = ???
5. Regulated PM delivery
- coat = ??? |
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Term
| Secretion from the trans-Golgi - Clathrin/AP coated vesicles |
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Definition
Two coat layers
- inner coat: adapter proteins (AP)
- outer coat: Clathrin
- vesicle pinching: Dynamin |
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Term
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Definition
- complex of 4 subunits
- each complex ~ 340 kDa
- form the 'inner' coat
- bind to the cytoplasmic segments of integral cargo and receptor proteins
- determines cargo |
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Term
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Definition
| trans-Golgi/late endosome-lysosome |
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Term
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Definition
| PM/late endosome-lysosome |
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Term
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Definition
| direction trans-Golgi to lysosomes |
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Term
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Definition
pinches off vesicle
- GTPase activity (requires GTP hydrolysis) |
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Term
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Definition
cell eating
- engulfment of large particles into large vesicles (>250nm)
- usually dones by specialized phagocytic cells (e.g. macrophages) |
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Term
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Definition
cell drinking
- ingestion of fluid and molecules in small vesicles (<150nm) |
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Term
| Step 1. of Receptor-mediated Endocytosis of LDL |
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Definition
- LDL receptor binds ApoB protein
- LDL receptor tails has AP2 sequence(NPXY sorting signal)
- LDL receptor binds AP2 |
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Term
| Step 2. of Receptor-mediated Endocytosis of LDL |
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Definition
- clathrin-coated pits invaginate
- clathrin-coated pits pinch off
- coated vesicles lose coat
- vesicles fuse with early endosomes |
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Term
| Step 3. of Receptor-mediated Endocytosis of LDL |
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Definition
- fuse with late endosomes (pH 5.0)
- lower pH releases liposome from the LDL receptor |
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Term
| Step 4. of Receptor-mediated Endocytosis of LDL |
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Definition
- LE fuses with lysosome
- Lysosomes break proteins and lipids into component parts; cholesterol integrates into cell membranes |
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Term
| Ste 5. of of Receptor-mediated Endocytosis of LDL |
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Definition
- LDL receptor is recycled to PM
- neutral pH reconfigures the receptor
- LDL receptor binds new LDL particles |
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Term
| Familial Hypercholesterolemia (FH) |
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Definition
first inherited disorder linked to myocardial infarctions
- mutations in the LDL receptors (5 distinct classes of mutations)
- autosomal dominant disease
- heterozygotoes: 1 in 500 individuals (very common)
- marked increases in cholesterol and LDL |
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Term
| Clinical consequences of FH |
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Definition
- hypercholesterolemia
- atherosclerotic plaque formation
- premature coronary artery disease
- myocardial infarctions
(homozygotes generally die <30 y.o. |
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Term
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Definition
1. Null mutations
2. LDL receptor remains in ER
3. NO receptor binding to LDL
4. NO LDL receptor internalization
5. NO LDL release and receptor recycling |
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Term
| Mechanism of phagocytosis - macrophages |
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Definition
- particle engages the surface of the macrophage
- surface receptors are bound, clustered and activated
- macrophages send up pseudopods to engulf the particle
- following engulfment, the phagosome fuses with a lysosome
- the lysosome digests the contents |
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