Lecture 16 endocytosis 2 Flashcards
What is the cause of familial hypercholesterolemia?
receptor for LDL is mutated resulting in higher concentration of blood cholesterol. It is a dominant trait which is exacerbated by having 2 of the same allele.
What part of the receptor is defective during familial hypercholesterolemia.
Some individuals with FH have normal receptor binding properties but are unable to be endocytosed into clathrin-coated pits. This is because mutation is on the cytoplasmic tail of the LDL receptor which is essential for AP2 binding.
The cytoplasmic tail contains a tyrosine based motif which can be recognized by the AP2 adaptor.
Is ligand binding necessary for formation of clathrin-coated pits?
No, clathrin coated pits form regardless of whether they are bound to a ligand or not in the case of some receptors. This is the case with LDL.
*receptors with the YxxΦ motif come together when clathrin coated pits begin to form. This isn’t the case, however, with EGF receptors (they are destroyed).
What is the sorting function of the early endosome?
Early endosome sorts receptors from the contents of fusing vesicle. This is done by sorting their location into different sites of the endosome. receptors are recycled from tubular endosome and content of vesicle is added to vesicular body.
What causes separation of ligand from receptor in the early endosome?
Separation of ligand from receptor occurs due to the lower pH of the early endosome (H+- ATPase pump)
How is LDL ultimately broken down in the cell?
Early endosome fuses with the lysosome to separate cholesterol from the protein of the LDL molecule.
What happens to proteins when added into the early endosomes?
Early endosomes receive incoming uncoated endocytic vesicles and sort it via 2 domains (vesicle body and tubular extensions).
How are endosomes differentiated from other compartments?
Certain proteins are specifically found in endosomes that differentiates them from other compartments.
How are multivesicular bodies formed?
Vesicles coming from early endosomes form multivesicular bodies when they fuse together and transform.
What is the function of multivesicular bodies?
They transport material from early to late endosome.
What is the function of multivesicular bodies?
They move along MTs and fuse with existing late endosomes.
What is different about the way EGF receptors are endocytosed compared to LDL?
They accumulate in clathrin coated pits only after binding to ligand.
The receptors themselves are not recycled but instead are degraded by lysosomes.
How are EGF receptors destroyed?
Exposed region contains ubiquitin. It is invaginated to form an internal vesicle within the multivesicular body.
Vesicle containing lipase and protease fuses with the multivesicular body and forms a lysosome.
How does the invagination of the membrane of the endosome occur to form the multivesicular body?
1) Hrs directs loading of specific cargo into vesicle buds. Hrs contains ubiquitin.
2) Hrs recruits cytosolic ESCRT to the membrane.
3) ESCRT complexes mediate invagination and fission of vesicles.
4) ESCRT complexes are disassembled from the membrane by Vsp4 which is an ATPase.
How are late endosomes formed?
Late endosomes receive transport vesicles from early endosomes. Multivesicular bodies formed by early endosomes results in the formation of late endosomes.
