Delidow - Endocytosis and Clinical Correlates

Question 1

Clathrin-mediated Endocytosis

Answer 1

Mechanism for selective uptake of specific macromolecules

Question 2

Where does endocytosis occur?

Answer 2

Calthrin-coated pits

Question 3

What aids in clathrin coated pits budding?

Answer 3

Dynamin

Question 4

What does the budding of clathrin coated pit form?

Answer 4

clathrin coated vesicle

Question 5

What do vesicles fuse with?

Answer 5

Early endosomes

Question 6

What are two fates for clathrin-coated vesicles once fused with early endosomes?

When does sorting occur?

Answer 6

1. Recycled to plasma membrane
2. Remain in early endosome (eventual degradation)

Sorting occurs from fusion with early endosomes happen

Question 7

What maintains the acidic pH of early endosomes?

What does pH change lead to?

Answer 7

Membrane proton pumps

Stripping receptor from ligand

Question 8

How is most of the internalized membrane replaced?

Answer 8

Recycling

Question 9

What type of endocytosis does not involve specific membrane receptors or coated pits?

Examples?

Answer 9

Clathrin-independent Endocytosis

Ex: Macropinocytosis and internalization of caveolae

Ex: Uptake of GPI-anchored plasma membrane proteins clustered in lipid rafts

Question 10

How is cholesterol mostly transported through the bloodstream?

What does uptake require?

Answer 10

Low-Density Lipoprotein (LDL) particles

Binding to specific receptors in clathrin-coated pits

Question 11

What can limit endocytosis (ex cholesterol)?

Where are these found?

Answer 11

Mutations that prevent LDL receptors from concentrating in coated pits

Found in the Internalization Signal in the cytoplasmic tail of the receptor

Question 12

What are the consequences of LDLR mutations?

Answer 12

Loss of ability to clear LDL from circulation, accumulation of vascular cholesterol, plaque and inflammation, CVD

Question 13

What is purpose of Alpha-1 Antiprotease (AP)

What does loss of function lead to?

Answer 13

Serpin w/ circulates to inhibit neutrophil elastase

Unopposed protease action against elastase in lung; made worse by smoking them marlboro red boizzz

Emphysema can onset at 30-40 in homozygotes

Question 14

What is most severe a1AP mutation?

Where is it made?

Answer 14

Z-Allele

Glu-Lys (negative to positive)

Liver disease in infants and children, due to aggregation in liver; inability to secrete adequate amount for protease inhibition

Made in the E.R. (product for secretion)

Question 15

CEDNIK Syndrome

Symptoms?

Cause?

Defects?

Answer 15

Early presentation, neurologic/psycho motor delays, misformed face, harder skin, early mortality

Autosomal recessive mutation SNAP29 (SNARE complex)

Failed Endocytosis, Failed Secretion

Question 16

I-Cell Disease

Symptoms?

Cause?

Defects?

Answer 16

Mucolipidosis; coase facial features, joint limitations, early death, skeletal abnormalities

Autosomal recessive, mutation in GNPTAB gene (tagging enzymes for lysosome)

Lysosomal enzymes fail to be incorporated into lysosomes, failure of lysosomal function

Question 17

What are the three types of membrane specification?

Answer 17

1. CC Pits
2. Caveolae
3. Lipid Rafts