Module 8 Flashcards

(51 cards)

1
Q

What is exocytosis?

A

Process of vesicle fusion with the plasma membrane to release contents outside the cell.

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2
Q

What is endocytosis?

A

Uptake of part of the plasma membrane to bring substances into the cell.

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3
Q

What is clathrin-mediated endocytosis?

A

A well-studied endocytic pathway involving clathrin and dynamin for internalizing substances.

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4
Q

What is the role of caveolae in endocytosis?

A

Caveolae are lipid-raft structures that internalize substances, respond to lipids, and can sense membrane tension.

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5
Q

What diseases are associated with caveolae dysfunction?

A

Lipodystrophy, pulmonary arterial hypertension, muscular dystrophies, and cancer-related roles.

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6
Q

What are clathrin-independent endocytic carriers (CLICs)?

A

Pathways for GPI-anchored protein endocytosis, fluid uptake, and cellular responses to stress, independent of clathrin.

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7
Q

What is macropinocytosis?

A

Engulfment of large membrane areas, often stimulated by growth factors, allowing for nutrient uptake in cancer cells.

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8
Q

How does phagocytosis function?

A

Engulfment of large particles like pathogens, requiring actin, followed by digestion in lysosomes.

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9
Q

What is the role of endosomes in the endocytic pathway?

A

Early endosomes sort internalized receptors; late endosomes further process them before delivery to lysosomes for degradation.

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10
Q

How can we study endocytosis?

A

Use of microscopy with specific markers, assays to track internalization routes, and perturbation of key components with inhibitors.

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11
Q

What markers are commonly used in studying endocytic pathways?

A

Transferrin, Cav1, Dextran, various receptor markers, and bacterial markers for identifying different endocytic routes.

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12
Q

What is the classical example of receptor trafficking studied?

A

Epidermal Growth Factor Receptor (EGFR) trafficking through endosomal compartments.

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13
Q

What are clathrin-coated pits (CCPs)?

A

Specialized structures on the plasma membrane involved in receptor-mediated endocytosis.

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14
Q

Who were the pioneers in the study of clathrin-coated pits?

A

Brown and Goldstein (Nobel Prize in 1985).

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15
Q

What is the role of LDL receptors in familial hypercholesterolemia (FH)?

A

LDL receptors bind low-density lipoproteins (LDL) for cholesterol uptake; their clustering in CCPs is impaired in FH.

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16
Q

What mutation affects LDL receptor clustering in FH?

A

Class 4 LDL-R mutation inhibits clustering due to a defect in the cytoplasmic domain.

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17
Q

What key components make up clathrin-coated vesicles?

A

Clathrin heavy and light chains form triskelion structures that assemble into cages.

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18
Q

What does cryo-electron microscopy (CryoTEM) reveal about clathrin?

A

It allows for high-resolution imaging and structural analysis of clathrin assemblies.

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19
Q

How does epsin contribute to clathrin-coated pit formation?

A

Epsin binds phosphatidylinositol (PI(4,5)P2) and recruits clathrin, promoting membrane invagination.

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20
Q

What are adaptor proteins, and what is their role in CCPs?

A

Adaptor proteins (like AP2) link clathrin to the cytoplasmic domains of receptors, facilitating coat formation.

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21
Q

How do phosphoinositides regulate protein trafficking?

A

They serve as platforms for recruiting proteins like AP2 and dynamin, critical for CCP formation.

22
Q

What is the function of synaptojanin in clathrin-coated vesicle dynamics?

A

Synaptojanin is a phosphatase that removes phosphate from PIP2, necessary for efficient coat disassembly.

23
Q

What is the role of dynamin in clathrin-coated pit budding?

A

Dynamin is a GTPase that forms oligomeric rings at the neck of budding vesicles, facilitating membrane fission.

24
Q

What happens during the uncoating of clathrin-coated vesicles?

A

Uncoating is energy-dependent, requiring Hsc70 and auxillin, along with synaptojanin for coat disassembly.

25
What are the pathways in protein trafficking?
LDL, TfR, EGFR, Mannose-6-phosphate Receptor.
26
How is the EGF receptor degraded?
EGF binding leads to phosphorylation, internalization via clathrin-coated pits, fusion with early endosomes, and lysosomal degradation.
27
What do Rab proteins do?
Regulate docking and translocation in vesicle trafficking.
28
What is the role of ESCRT proteins?
Form intralumenal vesicles and aid in membrane remodeling and cytokinesis.
29
How does EGFR downregulation relate to cancer?
Its degradation switches off proliferative signals; disruption can lead to unregulated growth.
30
Why is APP trafficking important in Alzheimer's disease?
Defective trafficking can increase toxic Aβ peptide production, worsening the disease.
31
What are exosomes?
Membrane vesicles that carry signals or cargo for cell-to-cell communication.
32
How do GLUT4 defects affect insulin resistance?
Impaired trafficking leads to reduced glucose uptake.
33
What is Rab5's significance?
Regulates early endosome fusion and cargo sorting.
34
How are Rab proteins studied?
Through localization, functional assays, and in vitro reconstitution.
35
What are lysosomes?
Membrane-bound organelles enriched in digestive enzymes for degrading cellular material.
36
What do lysosomes break down?
Proteins into amino acids, carbohydrates into simple sugars, and complex lipids into fatty acids.
37
What maintains lysosomal pH?
H+ ATPase pumps (vacuolar-ATPase) maintain a low pH of ~4.5-5.0.
38
How do lysosomes contribute to nutrient generation?
They generate nutrients for the cell or secrete degraded contents by fusing with the plasma membrane.
39
What is receptor internalization?
Internalization of receptors via clathrin-coated pits, with proteins sorted through the endolysosomal system.
40
What diseases are associated with lysosomal dysfunction?
Lysosomal storage diseases and cellular cholesterol disorders.
41
How are newly synthesized lysosomal enzymes delivered?
Via mannose-6-phosphate receptors that regulate trafficking and recycling.
42
What happens in mucolipidosis type II/III?
Defective GlcNAc-phosphotransferase leads to mis-sorting and hypersecretion of lysosomal enzymes.
43
What is Niemann-Pick disease type C?
A disorder caused by NPC1/2 loss, leading to cholesterol accumulation in lysosomes.
44
What is autophagy?
A critical degradation pathway for cellular survival, differentiation, and homeostasis, involving three types: macroautophagy, microautophagy, and chaperone-mediated autophagy.
45
What are the functions of autophagy?
Removal of proteins/organelles, nutrient generation during starvation, cellular component turnover, and clearance of diseases.
46
What is non-selective autophagy?
Degradation of cellular components for energy production during nutrient deprivation.
47
How is autophagy induced?
By starvation or damage signals, with the formation of isolation membranes derived from the ER.
48
What are the roles of PINK1 and Parkin in autophagy?
PINK1 accumulates on damaged mitochondria to recruit Parkin, which ubiquitinates substrates for degradation via autophagy.
49
How is autophagy related to Alzheimer's disease?
Defective autophagy leads to accumulation of autophagic vacuoles, Aβ plaques, and Tau tangles.
50
What is the role of autophagy in Parkinson's disease?
Autophagy is essential for degrading damaged mitochondria; mutations in PINK1 and Parkin affect this process.
51
How is autophagy studied?
Using transgenic mice with GFP-ATG and observing effects of ATG knockout at cellular and whole-animal levels.