Lysosomes Flashcards
How many lysosomes per cell?
100
What is the lysosome membrane described as?
Single membrane
What is the content in lysosomes described as?
Heterogenous content(Lots of different type of vesicles inside lysosomes
Examples of hydrolytic enzymes that lysosomes contain
○ Proteases ○ Lipase ○ Glycosidases ○ Nucleases ○ Phosphatases Sulfatases
How are the enzymes in lysosomes activated?
These enzymes are activated by proteolytic cleavage(the hydrolysis of peptide bond.
How are extracellular substrates delivered to lysosomes?
Fluid-phase endocytosis of molecules and lipoproteins (including receptor-mediated endocytosis)
What is the minimum size of phagocytosis of particles?
0.5um or more
What are the two ways intracellular substrates are delivered to lysosomes?
Microautophagy and macroautophagy
What is microautophagy, how it works and what is it induced by?
○ Microautophagy is the direct uptake of soluble or particulate cellular constituents
§ Cytoplasmic substances translocate into lysosomes by direct invagination of the lysosome membrane.
§ Induced by rapamycin which inhibits mTOR. This inhibition mimics cellular starvation resulting in autophagyIn
What is macroautophagy?
Macroautophagy is cytosol or organelles wrapped around in a membrane which then fuse with lysosomes.
What are the double membraned structures containing the material called?
Autophagosomes
How is non-selective macroautophagy activated?
Cellular starvation
What sort of transport is it across the lysosomal membrane?
Selective transport
Process of receptor mediated endocytosis
§ Specific receptors on the surface of the lysosomes bind to the extracellular molecule.
§ Plasma membrane region containing the receptor undergoes endocytosis forming a vesicle.
Molecules are transported to the lysosome and the receptors are recycled and placed back on to the cell membrane by exocytosis.
Targeting of lysosomal hydrolases to lysosomes
- Lysosomal enzymes are delivered to endosomes in vesicles that bud of the trans golgi network
- Lysosomal hydrolases recognised in the TGN due to M6P marker which are added to N-linked-oligosaccharides as the lysosomal enzyme pass through cis-golgi-network
- Transmembrane M6P receptor proteins are present in TGN and bind to the M6P at pH 5.6-5.7
The hydrolases are packaged in clathrin-coats (in the clathrin coated pits of the cystolic side) and bud off the TGN(in a coat called a retromer).
Protein glycosylation in the ER
- Translocation moves the incomplete oligosaccharide across the membrane and completion of the core oligosaccharide occurs within the lumen of the ER.
- Precursors which contribute mannose and glucose to the growing oligosaccharide in the lumen are dolichol phosphate derivatives
- The core oligosaccharide is transferred from the dolichol phosphate to an Asn residue of the protein within the ER.
The core oligosaccharide is further modified in the golgi and the five sugar residue are retained in the final N-linked oligosaccharide.
What is I cell disease due to?
Due to a single gene defect and is caused due to a recessive allele
What does I cell disease do to lysosomes?
• All the hydrolases are missing from the lysosomes and are found in the blood as they’re unable to sort properly
in the golgi apparatus
They are secreted out the cell rather than transported to the lysosomes
What defect in enzyme causes I cell disease?
• Due to defective or missing GIcNAc phosphotransferase
○ Lysosomal enzymes are not phosphorylated in the cis golgi network
○ The M6P receptors do not segregate them into appropriate transport vesicles in the TGN
Instead, the lysosomal hydrolases are carried to the cell surface and secreted
What are the symptoms of I cell disease?
- Skeletal abnormalities
- Developmental delay
- Enlarged liver and spleen
- Impaired hearing
- Death from pneumonia or congestive heart failure
