Lecture 2.2: Receptor Mediated Endocytosis Flashcards
What is Endocytosis?
It is the process by which substances enter a cell through the process of engulfment
What are the 3 Types of Endocytosis?
- Phagocytosis (cell eating)
- Pinocytosis (cell drinking)
- Receptor mediated endocytosis (RME)
Why is RME important?
It allows the internalisation of membrane receptors and their ligands via a membrane invagination process
What types of substances may be transferred in endocytosis?
- Nutrients
- Growth Factors
- Viruses
What is Phagocytosis?
It is the recognition, binding, internalization and destruction of large particles (cells, bacteria, viruses) >0.5μm
What cells specialise in Phagocytosis (Phagocytes)? (3)
- Macrophages
- Polymorphonuclear Neutrophils
- Dendritic Cells
What is the mechanism of phagocytosis?
- Pseudopodia form around the particle
forming a phagocytic vacuole. Also called a
phagosome - The phagosome fuses with a lysosome (or
late endosome) and form a
phagolysosome - Particle is hydrolysed
- Useful parts retained in cell, debris is
released from cell via exocytosis
How do phagocytes recognise pathogens?
They have PRRs which recognise PAMPs associated with microorganisms
What are PRRs?
Pattern Recognition Receptors
What are PAMPs?
Pathogen Associated Molecular Patterns
What are the 4 families of PRRs?
- Toll-like receptors (TLR)
- Nucleotide-binding oligomerization
domain-like receptors (NLR) - C-type lectin receptors (CLR)
- RIG-1 like receptors (RLR)
What does TLR4 recognise?
The lipopolysaccharide component of the cell wall of Gram-ve bacteria
What other receptors do Phagocytes have? Why are these important?
- Receptors for the Fc (heavy chain) end of
IgG molecules and for the C3b fragment of
complement - They use these to recogniSe and ingest IgG-
or C3b-coated targets
What is Opsonisation?
An immune process which uses opsonins (i.e. IgG) to tag foreign pathogens for elimination by phagocytes
What is another name for receptor mediated endocytosis?
Clathrin-dependent endocytosis
What is receptor mediated endocytosis?
It is the primary process by which cells internalise macromolecules such as hormones, enzymes, plasma proteins, cholesterol, iron…etc
What is the mechanism of receptor mediated endocytosis? (8 Steps)
1) Ligand binds to membrane receptor
2) Receptor-ligand migrates to clathrin-coated pit
3) Endocytosis
4) Vesicle loses clathrin coat
5) Receptors and ligands separate
6) Ligands go to lysosomes or Golgi for processing
7) Vesicle with receptors moves to the cell membrane
8) Transport vesicle and cell membrane fuse
(membrane recycling)
How is cholesterol transported in the blood?
In lipoproteins
What are Apolipoprotiens?
Apolipoproteins are proteins that bind to lipids (fats)
What is the role of Apolipoprotiens?
- To bind to and effectively solubilise lipids in
the blood - Combine with phospholipids to form
lipoprotein particles - Different lipids can be packed into these
- They also have a critical role as ligands
What Apolipoprotien is necessary for binding of LDL to LDL receptors and therefore its removal from circulation?
ApoB-100
What is Familial Hypercholesterolemia?
A genetic disease that causes high cholesterol levels in blood due to a defect in the LDL receptor (LDLR)
5 major classes of FH due to LDLR mutations: Class I
LDLR not synthesised
5 major classes of FH due to LDLR mutations: Class II
LDLR not transported from ER to Golgi for expression on the cell surface
5 major classes of FH due to LDLR mutations: Class III
LDLR does not bind LDL on cell surface because of a defect in either apolipoprotein B100 or in LDLR
5 major classes of FH due to LDLR mutations: Class IV
LDLR bound to LDL does not cluster in clathrin-coated pits for receptor mediated endocytosis
5 major classes of FH due to LDLR mutations: Class V
LDLR is not recycled back to the cell surface
What are the clinical presentations of hypercholesterolemia? (3)
Xanthelasma
Corneal Arcus
Xanthoma
What is Transferrin?
It is a plasma glycoprotein that reversibly binds iron
What is the role of Transferrin?
It is a major mediator of iron homeostasis
What is iron binding to Transferrin dependent on?
It is pH dependent, low pH reduces affinity and favours apotransferrin
Mode 1 of Receptor-Mediated Endocytosis: Fate of Receptor? Fate of Ligand? Example?
Receptor: Recycled
Ligand: Degraded
Example: LDL
Mode 2 of Receptor-Mediated Endocytosis: Fate of Receptor? Fate of Ligand? Example?
Receptor: Recycled
Ligand: Recycled
Example: Transferrin
Mode 3 of Receptor-Mediated Endocytosis: Fate of Receptor? Fate of Ligand? Example?
Receptor: Degraded
Ligand: Degraded
Example: Insulin, Epidermal growth factor Immune complexes
Mode 4 of Receptor-Mediated Endocytosis: Fate of Receptor? Fate of Ligand? Example?
Receptor: Transported
Ligand: Transported
Example: Maternal immunoglobulin G,
Secretory immunoglobulin A
What is Transcytosis?
It is the transport of molecules across the cytoplasm of a cell, it consists of endocytotic uptake and exocytotic release
How is B12 absorbed?
- B12 in mouth binds to haptocorrin
- HCl in the stomach separates vitamin B12 from the
protein that it’s attached to - The freed vitamin B12 then combines with a protein
made by the stomach, called intrinsic factor - The body absorbs them together in the gut
