BCH3021 Lecture Notes - Lecture 19: Cation-Dependent Mannose-6-Phosphate Receptor, Extracellular Fluid, Endosome
Lecture 19 – Vesicle Trafficking: Endocytosis
• Endocytosis: uptake of fluid, membrane and protein into the cell via specific
transport vesicles
o Means of recycling components of secretory apparatus
o Import of material from plasma membrane
• Cells initialize material from cell surface and extracellular environment
through endocytosis
• Primary endocytic sorting compartment is early endosome
• Defects in endocytosis → cause serious disease
Pathways Into Cell
• Phagocytosis
o Ingestion of large particles
• Macropinocytosis
o Ingestion of extracellular fluid and solutes
• Endocytosis
o Fluid phase (non selective)
o Adsorptive (partly selective)
o Receptor-mediated (selective)
▪ Cell decorates membrane with receptors → for ligands it must
interanlise
Secretory and Endocytic Pathways are linked
• Can transfer materials between organelles – linked
• Directions are different: secretory is out, endo is in
• E.g. trafficking of man-6-P receptor
o Besides delivery enzyems to lysosoems from TGN, M6PR retrieves
mis-directed lysosomal enzymes from cell surface via endocytosis
Endocytic vesicles carry material from exterior into the Cell
• Plasma membrane is dynamic
• Most cells continuously internalise membrane and proteins from cell surface
e.g. macrophages ingest 3% of plasma membrane per minute
• Spherical transport vesicles form at plasma membrane, encapsulating fluid,
membrane and proteins
• At least 3 distinct endocytic pathways into cell
o Clathrin-mediated endocytosis
▪ Most common and best understood pathway
o Caveolin-mediated endocytosis
o Clathrin/caveolin – independent endocytosis
Endocytic Vesicles go to the Early Endosome
• Internalised vesicles are uncoated and delivered to a
sorting organelle – early endosomeo
• Vesicles move from early endosome to
o Cell surface (recycling)
o Opposite surface in polarized cells – transcytosis
▪ Receptor-ligand pairs
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• Movement of cargo to lysosomes doesn’t require vesicles
Receptor – mediated endocytosis selectively enhances import efficiency
• Some proteins are efficiently directed into clathrin-coated transport vesicles
via receptors that associate specifically with vesicle
o Serves to concentrate the protein at sites of plasma membrane
internalization
▪ Can increase uptake of specific protein
o Receptor is often recycled to plasma membrane after release of cargo
protein (ligand) in early endosome
Transfer from Endosome to Lysosome does NOT involve transport vesicles
• Membranes of early endosomes invaginates to form multivesciluar bodies
(MVB) → MVB matures into late endosome → late endosome matures in
endolysosomes and lysosomes via progressive acidification or fusion with pre-
existing lysosomes
Stages and mechanisms of Receptor-mediated endocytosis
1. Formation of endocytic clathrin-coated vesicle around receptor and ligand
• Receptor on plasma membrane → interact with proteins involved with
formation of formation of vesicle
• Coat proteins can polymerise → force membrane to bend/curve →
form balloon
• Polymerised coat protein outside membrane
• Electron dense region: clathrin
2. Internalization and transport of vesicle to early endosome
• Receptor carries signal that tells if it is going to associate
• Receptors requires specific internalization sequences to associate with
endocytic vesicles
• Receptor is Transmembrane protein
o Region outside interacts with cargo molecule
o Region inside interacts with adaptin (protein)
▪ Interaction will only occur if there is a specific
sequence or structure on cytoplasmic tail of receptor
• Internalizing receptors carry a signal in the cytoplasmic domain
• Signal promotes binding to adaptors (adaptins) – which associate with
clathrin
find more resources at oneclass.com
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Document Summary
Pathways into cell: phagocytosis, ingestion of large particles, macropinocytosis, ingestion of extracellular fluid and solutes, endocytosis, fluid phase (non selective, adsorptive (partly selective, receptor-mediated (selective, cell decorates membrane with receptors for ligands it must interanlise. Interaction will only occur if there is a specific sequence or structure on cytoplasmic tail of receptor. Endocytic pathways are used as entry point by intracellular pathogens: most viruses and some microbes infect cells by endocytosis following binding to (hijacking) a cellular receptor, change in ph helps virus uncoat replicates in cytosol. Atherosclerosis inflammatory disease: hardening/blockage of arteries underpins heart disease, monocytes come to irritation site get rid of oxidised ldl cells die and. Uptake of cholesterol by endocytosis requires ldl receptor: excess ldl caused by, protein within ldl: apob-100 is recognised by ldl receptor on plasma membrane, receptor recycled to cell surface where it can be used again.
