Module 18

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Questions and Answers

What triggers the aggregation of molecules for secretory vesicles at low pH?

High calcium concentration

Increased ATP levels

Increased lysosomal enzyme activity

Low pH and calcium concentration (correct)

Which receptor is primarily responsible for the sorting of lysosomal hydrolases at the TGN?

Mannose-6-phosphate receptor (MPR) (correct)

Sortilin receptor

Insulin receptor

Phosphate receptor

What happens to clathrin-coated vesicles after they bud off from the TGN?

Clathrin is released during the budding process.

They immediately fuse with the plasma membrane.

Clathrin is lost before they reach the lysosome. (correct)

They retain the clathrin coat until fusion with the lysosome.

Which of the following is true about lysosomal acid hydrolases?

Their optimal pH is around 4.6. Signup and view all the answers

What is the role of GGA in lysosomal trafficking?

To bind and concentrate MPRs and other cargo in clathrin-coated vesicles. Signup and view all the answers

What is a common effect of chloroquine on Plasmodium parasites?

It increases the pH of the food vacuole and inactivates lysosomal acid hydrolases. Signup and view all the answers

What leads to the accumulation of undegraded substrates in lysosomal storage disorders?

Deficiencies in lysosomal enzymes. Signup and view all the answers

How do MPRs function at the plasma membrane?

They capture escaped secreted enzymes and return them to lysosomes. Signup and view all the answers

What role do proton pumps play in lysosomes?

They maintain an acidic environment critical for enzyme activity. Signup and view all the answers

Which of the following statements about the recruitment of ARF1 is correct?

ARF1 is a small GTPase that initiates vesicle formation. Signup and view all the answers

What is the major consequence of Tay-Sachs disease?

Death by around age three Signup and view all the answers

Which deficiency primarily leads to I-cell disease?

Phosphotransferase Signup and view all the answers

Which of the following correctly describes a feature of Niemann-Pick Type C disease?

Accumulation of cholesterol and glycolipids Signup and view all the answers

What role does the NPC1 protein play in the cell?

It transports cholesterol in the endosomal-lysosomal system Signup and view all the answers

What is the primary function of lysosomal acid hydrolases?

Digestion of cellular macromolecules Signup and view all the answers

What pH range is optimal for the functioning of lysosomal acid hydrolases?

Acidic (pH 4.6-5.0) Signup and view all the answers

Which disease is characterized by psychomotor retardation and skeletal deformities?

I-cell Disease Signup and view all the answers

What is a potential result of defects in lysosomal proteins?

Lysosomal storage diseases Signup and view all the answers

What initiates the sorting of proteins from the trans-Golgi network (TGN)?

Receptor-mediated sorting Signup and view all the answers

What is the effect of lysosomal storage diseases on cellular health?

Lead to cellular damage and potential death Signup and view all the answers

What is the initial cellular location where lysosomal proteins are synthesized?

Endoplasmic reticulum Signup and view all the answers

Which mechanism captures secreted enzymes for return to lysosomes?

Receptor-mediated endocytosis Signup and view all the answers

What happens to acid hydrolases when they are released from MPRs in the endosome?

They become active in the acidic environment Signup and view all the answers

What is the primary effect of chloroquine on Plasmodium parasites?

Increases the pH of food vacuoles Signup and view all the answers

Which structure corresponds to the budding of transport vesicles containing lysosomal enzymes?

Clathrin coat Signup and view all the answers

What is the consequence of deficiencies in lysosomal enzymes?

Accumulation of undegraded substrates Signup and view all the answers

Which component in lysosomal trafficking binds to small GTPase ARF1?

GGA Signup and view all the answers

What is the role of mannose-6-phosphate (M6P) tags on lysosomal enzymes?

To facilitate recognition by MPRs Signup and view all the answers

What is a major characteristic of lysosomes?

They are membrane-enclosed organelles with acidic pH Signup and view all the answers

Which protein is involved in the recruitment of MPRs to clathrin-coated vesicles?

GGA Signup and view all the answers

What is the consequence of a deficiency in hexosaminidase A in Tay-Sachs disease?

Accumulation of ganglioside GM2 Signup and view all the answers

Which of the following describes a characteristic feature of I-cell disease?

Accumulation of glycosaminoglycans Signup and view all the answers

Which protein dysfunction is associated with Niemann-Pick Type C disease?

NPC1 or NPC2 protein Signup and view all the answers

What is the main consequence of defects in lysosomal acid hydrolases?

Lysosomal storage diseases Signup and view all the answers

What role does the trans-Golgi network (TGN) play in protein sorting?

It facilitates receptor-mediated sorting Signup and view all the answers

What is the pH environment where lysosomal acid hydrolases function optimally?

Acidic (pH 4.6-5.0) Signup and view all the answers

Which mechanism primarily facilitates soluble protein sorting to lysosomes?

Sortilin/clathrin-mediated transport Signup and view all the answers

What is the outcome of the phosphotransferase deficiency in I-cell disease?

Increased levels of glycosaminoglycans Signup and view all the answers

What is a common feature of lysosomal storage diseases?

Build-up of macromolecules within cells Signup and view all the answers

What primarily causes death in Tay-Sachs disease?

Neurological degeneration Signup and view all the answers

What triggers the release of enzymes from their receptors in the endosome?

Decrease in endosomal pH Signup and view all the answers

What is the significance of M6P tags on lysosomal enzymes?

They aid in the recognition of enzymes by M6P receptors Signup and view all the answers

Which component is essential for forming clathrin-coated vesicles during lysosomal trafficking?

GGA adaptor protein Signup and view all the answers

How does chloroquine affect the lysosomes of Plasmodium parasites?

Inhibits the proton pumps, raising the lysosomal pH Signup and view all the answers

Which aspect of lysosomal function is primarily affected by lysosomal storage disorders?

Accumulation of undegraded substrates Signup and view all the answers

What facilitates the initial formation of clathrin-coated vesicles at the trans-Golgi network?

Recruitment of small GTPase ARF1 Signup and view all the answers

What characteristic feature do lysosomes maintain to ensure the functionality of their enzymes?

Acidic internal pH through proton pumps Signup and view all the answers

Which of the following correctly describes the consequence of not having MPRs on the plasma membrane?

Accumulation of enzymes outside lysosomes Signup and view all the answers

What type of receptor-mediated sorting targets lysosomal proteins via clathrin?

Sortilin Signup and view all the answers

What is the primary action of H+-ATPase pumps in lysosomes?

Concentrate protons to maintain acidic pH Signup and view all the answers

What results from a deficiency in phosphotransferase in I-cell disease?

Failure to properly package acid hydrolases Signup and view all the answers

What is the main consequence of lysosomal storage diseases?

Accumulation of macromolecules causing cellular damage Signup and view all the answers

Which disease is characterized by an accumulation of ganglioside GM2?

Tay-Sachs disease Signup and view all the answers

What acidic environment is ideal for the function of lysosomal acid hydrolases?

pH 4.6-5.0 Signup and view all the answers

What causes the skeletal deformities associated with I-cell disease?

Defective intracellular protein transport Signup and view all the answers

What is the role of NPC1 in Niemann-Pick Type C disease?

Transporting cholesterol and glycolipids in lysosomes Signup and view all the answers

Which feature is typical of the storage of glycosaminoglycans in lysosomal storage diseases?

Accumulation of undigested material Signup and view all the answers

What mechanism is primarily responsible for sorting soluble proteins to lysosomes?

Mannose-6-phosphate tagging Signup and view all the answers

In which condition do lysosomes contain undigested glycosaminoglycans?

I-cell disease Signup and view all the answers

Which protein is affected in Niemann-Pick Type C disease leading to cholesterol accumulation?

NPC1 Signup and view all the answers

Study Notes

Protein Sorting at the TGN

Receptor-mediated sorting directs lysosomal hydrolases to lysosomes via M6P receptors and endosomes.
Sortilin and clathrin are used for another type of sorting to endosomes.
Proteins destined for secretory vesicles condense from immature storage granules (ISG) to mature storage granules (MSG) in low pH and Ca2+ conditions.
CARTS transport lysosomal proteins C and PAUF to the plasma membrane.

Lysosomal Proteins at the TGN

Mannose-6-phosphate (M6P) tags on lysosomal enzymes are recognized by mannose-6-phosphate receptors (MPRs).
Lysosomal enzymes travel from the TGN in clathrin-coated vesicles to endosomes and subsequently to lysosomes.
MPRs are present on the plasma membrane to retrieve secreted enzymes and return them to lysosomes.
Synthesis of lysosomal proteins occurs on ribosomes attached to the endoplasmic reticulum (ER).

Characteristics of Lysosomes

Lysosomes are membrane-bound organelles characterized by acidic pH maintained by proton pumps.
They contain acid hydrolases, recognized by MPRs via their M6P tags.
Clathrin-coated vesicles bud off from the TGN, encapsulating enzymes and receptors.
Acidic conditions in endosomes lead to enzyme release from MPRs after clathrin shedding.

Lysosomal Trafficking Process

Vesicle formation is initiated by recruiting the small GTPase ARF1.
Clathrin-coated vesicles from the TGN include the adaptor protein GGA, which binds ARF proteins and MPRs.
Concentration of MPRs in clathrin-coated vesicles occurs through protein interactions.
Following budding, vesicles lose their clathrin coat before fusion with endosomes.

Proton (H+) Pumps in Lysosomes

The optimal functioning pH for acid hydrolases is 4.6, facilitated by H+-ATPase pumps.
The lysosomal membrane is protected by highly glycosylated integral membrane proteins.

Lysosomes in Malaria

Four Plasmodium parasite species are responsible for the majority of malaria infections.
Symptoms include flu-like indications and febrile attacks as parasite numbers rise in the bloodstream.
Untreated malaria may become chronic; chloroquine acts by raising pH and inactivating lysosomal acid hydrolases in the food vacuole of Plasmodium.

Lysosomal Storage Disorders

Lysosomal enzyme deficiencies lead to substrate accumulation, resulting in ~40-50 genetic disorders linked to storage issues.
Such disorders predominantly affect the nervous system’s function.
Tay-Sachs disease is marked by hexosaminidase A deficiency, leading to GM2 ganglioside accumulation, causing brain cell membrane issues and early death.

I-cell Disease

Characterized by psychomotor retardation and skeletal deformities, with lysosomes containing undigested glycosaminoglycans and glycolipids.
A defect in phosphotransferase causes inadequate packaging of acid hydrolases into lysosomes.

Niemann-Pick Type C Disease

Resulting from mutant NPC1 or NPC2 proteins, it leads to cholesterol and glycolipid accumulation in lysosomes.
NPC1 plays a crucial role as a transporter within the endosomal-lysosomal system.

Summary of Intracellular Transport

Protein sorting from the TGN involves receptor-mediated mechanisms and sorting for secretion or lysosomes through various pathways.
Lysosomes facilitate the action of acid hydrolases under acidic conditions; defects may lead to lysosomal storage diseases causing cellular damage and early mortality.

Protein Sorting at the TGN

Receptor-mediated sorting directs lysosomal hydrolases to lysosomes via M6P receptors and endosomes.
Sortilin and clathrin are used for another type of sorting to endosomes.
Proteins destined for secretory vesicles condense from immature storage granules (ISG) to mature storage granules (MSG) in low pH and Ca2+ conditions.
CARTS transport lysosomal proteins C and PAUF to the plasma membrane.

Lysosomal Proteins at the TGN

Mannose-6-phosphate (M6P) tags on lysosomal enzymes are recognized by mannose-6-phosphate receptors (MPRs).
Lysosomal enzymes travel from the TGN in clathrin-coated vesicles to endosomes and subsequently to lysosomes.
MPRs are present on the plasma membrane to retrieve secreted enzymes and return them to lysosomes.
Synthesis of lysosomal proteins occurs on ribosomes attached to the endoplasmic reticulum (ER).

Characteristics of Lysosomes

Lysosomes are membrane-bound organelles characterized by acidic pH maintained by proton pumps.
They contain acid hydrolases, recognized by MPRs via their M6P tags.
Clathrin-coated vesicles bud off from the TGN, encapsulating enzymes and receptors.
Acidic conditions in endosomes lead to enzyme release from MPRs after clathrin shedding.

Lysosomal Trafficking Process

Vesicle formation is initiated by recruiting the small GTPase ARF1.
Clathrin-coated vesicles from the TGN include the adaptor protein GGA, which binds ARF proteins and MPRs.
Concentration of MPRs in clathrin-coated vesicles occurs through protein interactions.
Following budding, vesicles lose their clathrin coat before fusion with endosomes.

Proton (H+) Pumps in Lysosomes

The optimal functioning pH for acid hydrolases is 4.6, facilitated by H+-ATPase pumps.
The lysosomal membrane is protected by highly glycosylated integral membrane proteins.

Lysosomes in Malaria

Four Plasmodium parasite species are responsible for the majority of malaria infections.
Symptoms include flu-like indications and febrile attacks as parasite numbers rise in the bloodstream.
Untreated malaria may become chronic; chloroquine acts by raising pH and inactivating lysosomal acid hydrolases in the food vacuole of Plasmodium.

Lysosomal Storage Disorders

Lysosomal enzyme deficiencies lead to substrate accumulation, resulting in ~40-50 genetic disorders linked to storage issues.
Such disorders predominantly affect the nervous system’s function.
Tay-Sachs disease is marked by hexosaminidase A deficiency, leading to GM2 ganglioside accumulation, causing brain cell membrane issues and early death.

I-cell Disease

Characterized by psychomotor retardation and skeletal deformities, with lysosomes containing undigested glycosaminoglycans and glycolipids.
A defect in phosphotransferase causes inadequate packaging of acid hydrolases into lysosomes.

Niemann-Pick Type C Disease

Resulting from mutant NPC1 or NPC2 proteins, it leads to cholesterol and glycolipid accumulation in lysosomes.
NPC1 plays a crucial role as a transporter within the endosomal-lysosomal system.

Summary of Intracellular Transport

Protein sorting from the TGN involves receptor-mediated mechanisms and sorting for secretion or lysosomes through various pathways.
Lysosomes facilitate the action of acid hydrolases under acidic conditions; defects may lead to lysosomal storage diseases causing cellular damage and early mortality.

Protein Sorting at the TGN

Receptor-mediated sorting directs lysosomal hydrolases to lysosomes via M6P receptors and endosomes.
Sortilin and clathrin are used for another type of sorting to endosomes.
Proteins destined for secretory vesicles condense from immature storage granules (ISG) to mature storage granules (MSG) in low pH and Ca2+ conditions.
CARTS transport lysosomal proteins C and PAUF to the plasma membrane.

Lysosomal Proteins at the TGN

Mannose-6-phosphate (M6P) tags on lysosomal enzymes are recognized by mannose-6-phosphate receptors (MPRs).
Lysosomal enzymes travel from the TGN in clathrin-coated vesicles to endosomes and subsequently to lysosomes.
MPRs are present on the plasma membrane to retrieve secreted enzymes and return them to lysosomes.
Synthesis of lysosomal proteins occurs on ribosomes attached to the endoplasmic reticulum (ER).

Characteristics of Lysosomes

Lysosomes are membrane-bound organelles characterized by acidic pH maintained by proton pumps.
They contain acid hydrolases, recognized by MPRs via their M6P tags.
Clathrin-coated vesicles bud off from the TGN, encapsulating enzymes and receptors.
Acidic conditions in endosomes lead to enzyme release from MPRs after clathrin shedding.

Lysosomal Trafficking Process

Vesicle formation is initiated by recruiting the small GTPase ARF1.
Clathrin-coated vesicles from the TGN include the adaptor protein GGA, which binds ARF proteins and MPRs.
Concentration of MPRs in clathrin-coated vesicles occurs through protein interactions.
Following budding, vesicles lose their clathrin coat before fusion with endosomes.

Proton (H+) Pumps in Lysosomes

The optimal functioning pH for acid hydrolases is 4.6, facilitated by H+-ATPase pumps.
The lysosomal membrane is protected by highly glycosylated integral membrane proteins.

Lysosomes in Malaria

Four Plasmodium parasite species are responsible for the majority of malaria infections.
Symptoms include flu-like indications and febrile attacks as parasite numbers rise in the bloodstream.
Untreated malaria may become chronic; chloroquine acts by raising pH and inactivating lysosomal acid hydrolases in the food vacuole of Plasmodium.

Lysosomal Storage Disorders

Lysosomal enzyme deficiencies lead to substrate accumulation, resulting in ~40-50 genetic disorders linked to storage issues.
Such disorders predominantly affect the nervous system’s function.
Tay-Sachs disease is marked by hexosaminidase A deficiency, leading to GM2 ganglioside accumulation, causing brain cell membrane issues and early death.

I-cell Disease

Characterized by psychomotor retardation and skeletal deformities, with lysosomes containing undigested glycosaminoglycans and glycolipids.
A defect in phosphotransferase causes inadequate packaging of acid hydrolases into lysosomes.

Niemann-Pick Type C Disease

Resulting from mutant NPC1 or NPC2 proteins, it leads to cholesterol and glycolipid accumulation in lysosomes.
NPC1 plays a crucial role as a transporter within the endosomal-lysosomal system.

Summary of Intracellular Transport

Protein sorting from the TGN involves receptor-mediated mechanisms and sorting for secretion or lysosomes through various pathways.
Lysosomes facilitate the action of acid hydrolases under acidic conditions; defects may lead to lysosomal storage diseases causing cellular damage and early mortality.

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Description

This quiz focuses on the mechanisms involved in sorting proteins at the trans-Golgi network (TGN), including receptor-mediated sorting and the aggregation of proteins for secretory vesicles. It explores the transport of lysosomal proteins and the role of low pH and calcium in protein maturation. Test your understanding of these critical processes in cellular biology.