Golgi membranes are absorbed into and reemerge from the ER during mitosis
Post-Translational Events II ER & Golgi Processes.
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Transcript of Post-Translational Events II ER & Golgi Processes.
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Post-Translational Events II
ER & Golgi Processes
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Rough Endoplasmic Reticulum
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Glycolsylation• O-linked – serine, threonine, hydroxylysine (collagen)• N-linked - asparagine• The sugars
– GalNac – N-acetylgalactosamine– GlcNac – N-acetylglucosamine– NANA – N-acetylneuraminic acid (sialic acid)– Gal – galactose– Glc – glucose– Man – mannose– Fuc – fucose– Dolicholpyrophosphoryl oligosaccharide
• All sugars are linked to nucleoside mono- or diphosphate– UDP-gal, UDP-GalNac, UDP-GlcNac– GDP-man– CMP-NANA– Dolichol pyrophosphate
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Glyco-nucleoside Phosphates
CH3C(CH3)=CHCH2 CH2C(CH3)=CHCH215-18CH2CH(CH3)CH2CH2OPO3
Dolichol phosphate
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O-linked Glycosylation
• Small chains of sugars• N-acetylgalactosamine (GalNac) is first sugar on
S orT– GalNac transferase in ER and cis-golgi
• Additional sugars added in cis, medial and trans-golgi– Gal added by galactosyl transferase– NANA added last
• Each sugar addition is catalyzed by specific enzyme
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N-linked Glycosylation
• Initial step in ER• Dolichol pyrophosphoryl oligosaccharide
– 14 sugar moiety attached to dolichol pyrophosphate• (GalNac)2Man9Glc3
– Dolichol phosphate in ER membrane– Sugars added by cytostolic glycosyltransferases– Moiety flips in ER membrane to face lumen– Transferred to asparagine by oligosaccharyl transferase
(oligosaccharide-protein transferase)– Target sequence N-X-S and N-X-T (X = P)
• Subsequent remodeling of sugar moiety in ER & golgi• N-linked chains very long and extensively branched
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O- & N-linked Oligosaccharide
Chains
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N-linked Glycolsylation
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GPI – Linkages
• GPI – linked proteins are attached to GPI in ER– GPI in ER membrane– C-term of protein attached to sugar residue on
phosphatidyl inositol
• GPI linked protein will be attached to outer leaflet of plasma membrane
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Protein Folding Occurs in ER Lumen
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Misfolded Proteins Reverse Translocate to Proteasome
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Unique Signaling from ER to Make More ER• Pathway activated by stresses that result in more unfolded
proteins–heat–unfavorable pHs
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On to the Golgi
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Processing in the Golgi
• Oligosaccharide modifications• Sorting to exocytic vesicles, lysosomes and ER• Proteolytic processing
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Modification of N-linked Oligosaccharides
• As glycosylated protein moves through ER Glc is removed
• In cis Golgi, some Man is removed• In medial golgi, GlcNac is added• In trans-golgi, Gal and NANA are
added
CIS TRANS
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Mannose-6-Phosphate is Lysosomal Targeting Signal
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Proteolytic Processing
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Sterol & Lipid Biosynthesis
• Phospholgycerides in ER• Sphingolipids in Golgi• Lipid profile asymmetry
established via phospholipid exchange proteins and selective vesicular transport due to association between carrier proteins and certain lipid types
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Regulation of HMG-CoA Reductase