BIOB10H3 Lecture Notes - Lecture 6: Clathrin, Endosome, Cell Membrane

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21 May 2018
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Lecture 6
Endocytosis and Phagocytosis
Cellular Uptake of Particles and Macromolecules
materials too large to pass through membrane
o eg. uptake of transporters and signaling receptors no longer required
o uptake of extracellular materials (ligands)
uptake occurs into cytoplasmic vesicles derived from invaginations of cell membrane
Two separate categories:
endocytosis
phagocytosis
Endocytosis
uptake of dissolved solutes, macromolecules, signaling receptors, etc.
Receptor-mediated endocytosis (RME)
uptake of specific extracellular macromolecules (ligands) that bind to receptors on external cell
membrane surface
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Take up hormones, growth factors, enzymes, plasma proteins by binding to receptors
Endocytic Pathway (receptor-mediated)
receptors bind ligand- undergo conformational change, clathrin binds on cytosolic side
PM pinches in (via clathrin) to form early endosome (EE)
early endosome matures into sorting compartment (SC)
sorting compartment lumen fluid acidified due to action of membrane H+ pumps
in low pH, ligands are released from cell membrane receptors
receptors are recycled back to cell membrane in vesicles
edosoe carrier esicles ECV’s leae “C ad fuse ith late endosomes (LE)
mature into lysosomes where contents are digested (via acid hydrolases)
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Document Summary

Endocytosis uptake of dissolved solutes, macromolecules, signaling receptors, etc. Receptor-mediated endocytosis (rme: uptake of specific extracellular macromolecules (ligands) that bind to receptors on external cell membrane surface. Take up hormones, growth factors, enzymes, plasma proteins by binding to receptors. Mature into lysosomes where contents are digested (via acid hydrolases) Phagocytosis (cell eating: receptors cluster into lipid rafts, clustering signals recruitment of signaling proteins. Pi3k (phosphorylates pi"s: pi3k phosphorylates pi on plasma membrane to make pi3p. Phagocytosis (cell eating: pi3p recruits ph-domain containing proteins, ph-proteins bind to actin proteins and cause the underlying actin cytoskeleton to rearrange, actin rearrangement causes large membrane extensions which engulf particle, particle internalized into membrane-bound compartment called phagosome. Phagocytosis (cell eating: phagosome fuses with lysosomes. Phagolysosome acid hydrolases kill/digest bacteria: so(cid:373)e pathoge(cid:374)s (cid:862)escape(cid:863) lysoso(cid:373)es, consequently are not killed and can proliferate in macrophages eg. mycobacterium, salmonella, pathogens secrete factors which interfere with rab proteins so lysosomes are not targetted correctly to phagosomes.

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