endomembrane system endomembrane system - people · 2016-03-15 · • endomembrane system •...
TRANSCRIPT
endomembrane system
chapter 15
internal membranes• endomembrane system
• functions as a coordinated unit• divide cytoplasm into distinct
compartments• controls exocytosis and
endocytosis• movement of molecules which
cannot pass through membrane
origins• endomembrane system
• invagination of plasma membrane• mitochondria
• endosymbiosis• chloroplasts
• endosymbiosis
transport of proteins• protein synthesis
• begins on a ribosome in cytoplasm
• sorting signals• protein transport
• nuclear transport• protein translocators• vesicular transport
pathways• endocytic
• endosomes & lysosomes• exocytic
• biosynthetic pathway• secretory pathway
• constitutive secretion• regulated secretion
• secretory granules
exocytic endocytic
golgi complex
rough ER
secretory granule
regulated secretory pathway
constitutive secretory pathway
endocytic pathway
endoplasmic reticulum• rough ER
• cisternae -• many bound ribosomes • polarity
biosynthesis in RER• synthesis of proteins
• free ribosomes• cytosolic proteins• peripheral proteins• nuclear proteins
• bound ribosomes• secretory proteins• integral proteins
Completed polypeptide
Incoming ribosomalsubunits
Start of mRNA (5′ end)
End of mRNA (3′ end)
Polyribosome
Ribosomes
mRNA
0.1 μm
Growingpolypeptides
biosynthesis in RER• bound ribosomes
• bind to ER as needed• SRP (signal recognition particle)• binds to SRP receptor
• translocon
Ribosome
mRNA
Signal peptide
SRP
1
SRP receptor protein
Translocationcomplex
ER LUMEN
2
3
45
6
Signal peptide
removed
CYTOSOL
Protein
ER membrane
biosynthesis in RER• translocon
• SRP interacts with a SRP receptor• ribosome interacts with the translocon• SRP is released
• facilitated by G-proteins
Ribosome
mRNA
Signal peptide
SRP
1
SRP receptor protein
Translocationcomplex
ER LUMEN
2
3
45
6
Signal peptide
removed
CYTOSOL
Protein
ER membrane
biosynthesis in RER• Processing
• signal sequence cleaved by signal peptidase• Carbohydrates added
• oligosaccharyltransferase• RER lumen
• chaperones assist in folding• protein disulfide isomerase adds disulfide bonds to
cysteines.
biosynthesis in RER• integral membrane proteins
• hydrophobic region generated• translocon opens laterally
• expels transmembrane segment• synthesis continues
biosynthesis in RER• glycosylation
• begins in the RER• membrane bound glycosyltransferases (GTs)
• lipid carrier (dolichol phosphate)• oligosaccharyltransferase -> transfers to polypeptide
• removal of 2 of 3 terminal glucose residues• quality control
• glycoprotein binds with calnexin (chaperone)• terminal glucose removed
• GTs recognize malfolded proteins• tag with glucose --> refolded or destroyed
• transferred to golgi
endoplasmic reticulum• smooth ER
• functions• synthesis of steroid hormones• liver processing of toxins• sequestration of Ca+
• sarcoplasmic reticulum
golgi bodies• golgi apparatus
• functionally distinct cisternae - • cis• trans
• differences in composition between cis and trans face
trans-Golgi network (TGN)
trans cisternae
medial cisternae
cis cisternae
cis- Golgi network
movement of materials• movement across Golgi
• vesicular transport model• vesicles shuttle cargo from
CGN to TGN • cisternal maturation model
• cisternae mature as they move through the apparatus
• combination?• retrograde transport via
vesiclescisternal vesicular
glycosylation• carbohydrate assembly
• glycolipids and glycoproteins• assembled across golgi by glycosyltranferases
vesicle shuttles• vesicle-mediated transport
• donor compartment• acceptor compartment• direction
• anterograde transport• toward plasma membrane
• retrograde transport• away from plasma membrane
• protein coats• two main functions
• cause membrane to curve• select components to be carried
vesicle shuttles• steps in vesicle transport
• (1) cargo selection• sorting mechanisms• coat proteins
• COPI, COPII, clathrin• bulk transport
• proteins trapped
Nat
ure
Rev
iew
s M
olec
ular
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10,
360
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ay 2
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vesicle shuttles• steps in vesicle transport
• (2) budding• coat proteins interact with adaptor proteins
• COPII - sec23/24, sec13/31, Sar1• Sar1 - coat recruitment GTPase
COPII
adaptor protein (Sar1)
protein cargo
cargo receptor
vesicle shuttles• steps in vesicle transport
• (3) scission• scission proteins excise bud
• (4) uncoating• coat proteins detach and get reused
protein cargo
vesicle shuttles• steps in vesicle transport
• (5) transport • microtubule transport via
motor proteins• dynactin
• (6) tethering• Rab proteins bind to tether
proteins on acceptor membrane
Rab
tethering proteins
x
vesicle shuttles• steps in vesicle transport
• (7) docking• soluble NSF attachment
protein receptor• v-SNAREs• t-SNAREs
• (8) fusion • (9) disassembly
• NSF and SNAP proteins
exocytic pathway• TGN
• proteins sorted• secretory (constitutive &
regulated)• lysosomal
• constitutive secretion• plasma membrane proteins
• polarized cells - apical / basal proteins segregated in TGN
non-lysosomal proteins• regulated secretion
• aggregate as dense granules at TGN• secretory vesicles (granules)• 2 main functions
• timing, amount
release of materials• exocytosis
• triggered by increase in Ca2+ • vesicle fuses with plasma
membrane• autophagy
• digestion of organelles• autophagosome
• organelle wrapped in double membrane
• fuses with lysosome• autophagolysosome
lysosome enzyme sorting• sorting proteins at TGN
• lysosomal proteins tagged• phosphorylated mannose• recognized by MPRs
• released in clathrin-coated vesicles
lysosomes• digestive organelles
• contain acid hydrolases• digest a wide variety of biological
molecules• intracellular digestion
Spongocoel
Osculum
Pore
Epidermis Waterflow
Mesohyl
Choanocyte
Spicules
Amoebocytes
lysosomal disorders• Tay-Sachs disease
• autosomal recessive disorder• probably with multiple origins
• deficiency in hexosaminidase A• buildup of ganglioside GM2
• symptoms include• mental retardation, blindness, death
uptake of materials• phagocytosis• endocytosis
• pinocytosis• receptor-mediated
endocytosis
RME• receptor-mediated endocytosis
• clathrin coat arranged in geometric pattern
lipoproteins on cell surface clathrin polygons
on inner surface
invagination of clathrin pit
clathrin structure• clathrin
• triskelion• three heavy chains• three light chains
• binds to AP2 adaptor• binds to cargo receptors
clathrin structure• clathrin
• triskelions and adaptors geometrically arranged
• dynamin-ring• promotes pinching off of coated
pit into vesicle• uses GTP to tighten around neck
of vesicle• Hsc70 uses ATP and frees clathrin
coat
endocytic pathway• endosomes
• formed from fusion of endocytes• sorts materials arriving from plasma
membrane• early endosomes
• derived from PM vesicles• fuse with early endosome• proteins dissociate - pH affects
conformation• proton pumps lower pH of endosome• late endosome • lysosome
metabolizing cholesterol• cholesterol packaging
• lipoproteins • LDLs and HDLs
• LDLs taken up by RME• lysosomes • release cholesterol for use
endothelial injurymacrophage
fibrous cap
engulfing particulate• phagocytosis
• engulfing large particles• phagosome
• fuses with lysosome• phagolysosome
engulfing particulate• phagocytosis
• cells of immune system• engulf foreign material• some pathogens can
withstand being phagocytized• Mycobacterium
tuberculosis• Coxiella burnetti• Listeria
monocytogenes