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Endomembrane system (Components: Membrane-enclosed (ER (Smooth ER (Drug…
Endomembrane system
Components: Membrane-enclosed
ER
Rough ER
Func
Folding of polypeptides
Recognition/removal of misfolded proteins
Addition of carbs to glycoproteins
Assembly of multimeric proteins
Smooth ER
Drug detoxifications
Lipid synthesis
Structures
Space inside sacs = ER lumen
Membr-bound sacs = ER cisternae
Endosomes
Nucleus
Lysosomes (see process)
Mitochondria & Chloroplast
Perixosomes
Golgi apparatus
Func: Membrane & protein trafficking
Structure: 2 faces
Cis-Golgi network (CGN): toward ER
Trans-Golgi network (TGN)
Medial cisternae: between TGN & CGN
Purpose: protein processings
Processes predicts lipids and proteins moved
Stationary cisternae model
Cisternal maturation model
Cytosol
Origin
Endosymbiosis theory
anaerobic pre-eukaryotic cell
engulged aerobic prokaryotic cell
Mitochondria
Ancient prokaryotic cell evolved to eukaryotic cell
Processes
Protein synthesis
Where: cytosol at free ribosomes
2 pathways after translation
Membr-bound ribosome cycle
Cotranslational Import
Purpose: export fr the cel
Signal hypothesis: ER signal sequence
Pur: directs mRNA to rER
Structure
15-30 amino acids long
N-terminal; hydrophobic region; polar region
mRNA
ER signal sequence
Signal recognition particle
Processes
mRNA
ER signal sequence
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Integral Membrane proteins
Where: synthesized on rER
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Free Ribosome cycle
Membrane biosynthesis
Where: Fatty acids in cytoplasm
Incorporated: ER membrane on cytosolic side
Phospholipid translocators (flippases)
Transferred to lumen side
Influenced by: membrane asymmetry
Glycosylation
2 kinds
O-linked
add sugar to Oxygen on hydroxyl group
Destination: serine or threonine
N-linked
add sugar to Nitrogen atom
Destination: asparagine residues
Know the picture slide 40
What: addition of carb side chains to proteins
Where: ER & Golgi
Terminal glycosylation
Where: Golgi
Processes
Removed few units of core oligosaccharide
Add GlcNAc or other monosaccharides
Galactosyl transferases to galactose
Quality control
Binding protein (BiP)/chaperone
prevents aggregation
ER-associated degradation (ERAD)
Where: rER
Target: incorrectly folded proteins
How: cytosolic proteasomes
Calnexin (CNX) & calreticulin
what: promote disulfide bond formation
Purpose: proper folding assistance
How: bind to monoglucosylated glycoproteins
Retention tag
sequence RXR (Arg-X-Arg)
Proteins localized to ER
Purpose: no escaping fr ER
Some proteins in plasma membrane
Retrieval tags
KDEL sequence
what: Lys-Asp-Glu-Leu
Destination: any proteins go to ER
How: receptor in Golgi sends proteins KDEL back to ER
HDEL
in yeast
What: receptor-ligand complex => vesicle => ER
Membrane Trafficking
Anterograde
Toward plasma membr = exocytosis
Significant: a bit of ER becomes plasma membr
Balance: lipds toward plasma mambrane
COPII: ER to ERGIC and Golgi
Retrograde
Vesicles fr CGN to ER
Balance: lipids toward plasma membr
COPI
fr ERGIC and Golgi backward to ER
Fr trans Golgi to cis Golgi
SLide 62 (good picture)
Coat Proteins
COPII
Anterograde
Clathrin
Receptor-Mediated Endocytosis
Struct: 2 multimeric proteins
adaptor protein (AP)
Clathrin
Benefit: driving force => induce flat membr => spherical vesicle
Uncoating a vesicle
Req: ATPase (Energy)
Clathrin dissociates rapidly
Process
Ligands bind to their receptors
diffuses laterally
encounter coated pits
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COPI
Retrograde
Table 12-2 slide 67
Lysosomal Proteins
Process
Tagged lysosomal proteins
binds mannose-6-phosphate receptors (MPR)
Conveyed to an endosome
Late endosomes
Transported fr TGN to organelles
form new lysosome
delivers its contents to active lysosome
Disease condition
I-cell disease: lysosomes = misdirected
Mannose-6-phosphate tag
Catalyzes by
2nd: mid-Golgi compartment => removes GlcNAc => leaving mannose-6-phosphate residue
1st: phosphotransferase => adds GlcNAc-1-phosphate to carbon 6 of mannose
Acid phosphatase & hydrolytic enzymes
How: ATP-dependent proton pumps
Acidic environment for lysosome
Know some example of enzymes
Func: degradation of external materials
Autophagy
Transporting material across plasma membrane
Endocytosis
Overall process
segment of plasma membrane folds inward
pinches off
endocytic vesicle
ex: phagocytosis; pinocytosis
Type of endocytosis
Receptor-mediate endocytosis (clathrin-dependent endocytosis)
See clathrin
Exocytosis
Secretory pathways
Outline
ER
Golgi
Secretory vesicle
Cell surface
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Types of secretion
Constitutive secretion
TGN
directly to cell surface
Unregulated process
Continuous & independent
Ex: mucus secretion of intestinal lining
Regulated secretion
Budding fr TGN
Immature secretory vesicles
Accumulated in cell
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Ex: Neurotransmitter release
Polarized secretion
limited to specific surface of the cell
ex: intestinal cells secrete digestive enzymes to 1 side of the cells