Download The endoplasmic reticulum and the Golgi

The endoplasmic reticulum and the Golgi
apparatus permit protein construction and
transport in a cell. 11/20
How are cells are divided into organelles for
localized specialization within a cell?
What pathways do proteins take post-translation
from mRNA to ribosomes in the RER and
cytosol?
How/where are proteins modified in a cell?
SER stores Ca++ and modify proteins.
How does a cell use the SER to create differences
in the PL content of its bilayers?
How does the Golgi Apparatus participate in
exocytosis and endocytosis?
How does clathrin help mediate receptormediated endocytosis?
Cellular compartmentalization allows for local
specialization in eukaryotic cells.
– Who we have seen:
 Nucleus: info stored here
 Mitochondria: power plant
 Chloroplast: powerplant
– Who we will see today:
 Endoplasmic reticulum: make protein here
– Also: store calcium, metabolize drugs, modify glycogen
 Golgi Apparatus: modify/export protein here
– Modify proteins for export here
 Vesicles and Endosomes: bulk entry/exit points into cell
– Who we won’t see much of….
 Lysosome: digest material inside cell
 Peroxisome: digest long chain fatty acids and bacteria
What pathways do newly transcribed proteins
take when going to their ultimate destinations?
ER folds have HUGE surface when spread out!
OPTION ONE:
1) mRNA finds a ribosome
on ER membrane:
Protein created2) Rough E.R.:
Protein sent into
lumen3) Golgi Apparatus:
Protein to 3 destinations:
a) Plasma membrane
b) Lysosome
c) Secretory Vesicles
Constituitive/Regulated
OPTION TWO:
1) mRNA find ribosome:
Protein created
2) Ribosome stays free in cytosol
Protein released to cytosol
3) Protein to intracellular destination
Huge holes in target let protein enter:
a) Nucleus:
b) Mitochondria
c) Chloroplast
d) Peroxisome
“Porins” permit entry into organelle

Basic Pathway: nucleus mRNA Ribosome:
ERCisGolgiGolgiCisternaeTrans-Golgi
Option Two: CytosolPoresTarget Organelle
Many proteins are modified when they are put
into the ER lumen after translation!
 Sequences are clipped off: Insulin
 Disulfide bonds may be added: Insulin
 Carbohydrates may be added: N-CAMS
 Amino Acids may be modified to modify protein
conformation: Hydroxylysine/Hydroxyproline
 Chaperones may fold nascent protein into
precise conformations: Hemoglobin
 Additional Modifications often take place in the
Golgi Apparatus
The smooth ER is devoid of ribosomes and helps
modify proteins and metabolize drugs/toxins.
Cytochrome P-450 reduces target molecules with electrons
taken from NADPH
Hepatocytes are really good at making NADPH
P-450 destroys carcinogens/toxins
System increases solubility/removal of metabolites
Water soluble toxins no longer reabsorbed
BASIC RXN:
R-H+NADPH+H++O2R-OH+NADP+H2O
Cells make more P-450 if stimulus continues!
This is called enzyme or P450 induction!
This cellular event explains why resistances to some drugs
develop over time! AIDS, Addiction, Alcoholism, Toxic
Resistance and why some drugs just stop working
The smooth ER also helps with calcium, lipid
transport, and carbohydrate metabolism.
Calcium can be stored in the SER
– Some SER rich in IP3-regulated channels/Ca-ATPase
– Exit from SER in response to signal transduction cascade
– Special muscle SER is called “Sarcoplasmic Reticulum”
– Tons of sarcoplasmic reticulum in cardiac/skeletal myocytes
– Keep cytosolic Ca in micromolar concentrations at rest
 SER enzymes regulate glycogen metabolism
cAMP-dependent glycogen phosphorylase here!
GlycogenG-1-PG-6-P
Why does muscle SER lack glucose-6-phosphorylase?
Why does hepatocyte SER have glucose-6-phosphorylase?
Phospholipids are not evenly stacked in the PL
bilayers of different cells/organelles
How do cells create lipid bilayers with differing
ratios of phospholipids? Membrane Asymetry is
critical for cellular/organelle functions!
 Lipid Bilayer content determines function!
– Ratio of different lipid types is important in disease!
 3-Glycerol kinase creates Phospholipids
 Lipids easily flip PLs across bilayer halves
 Lipids don’t easily flip from bilayerA to bilayerB
 Phospholipid Translocate (“Flippase”) allows
PL to be moved from SER into target bilayers
– Targets: Plasma membrane and nucleus
 PL Exchange protein moves specific PL to
membranes of organelles
– Targets: mitochondria, chloroplasts and peroxisomes.
The Golgi Apparatus is a massive organelle that
modifies and targets protein for export: SER
CicGolgi>MedialCisterna>TransGolgi>Export
Most proteins move directionally towards the plasma
membrane (Anterograde Tx)for secretion, sometimes
proteins move from PM to ER (Retrograde Tx).
Exocytosis :fusion of secretory vesicles with PM
Constituitive: happens at same rate all the time
Regulated: happens in response to stimulus (Ca)
How does this explain how
glucose transporters (GLUT) in
a vesicle reach the PM
following a meal and insulin
release?
Insulin StimulateTyrosineKinase
Kinase activated Phospholipase
Lipase releases IP3 into cytosol
IP3 opens SER Ca++-channels
Ca++ initiates V-fusion with PM
Vesicle GLUT now on PM
Glucose can enter the cell!
Receptor-mediated endocytosis permits a cell to
pull large particles inside after binding to
receptors that line clathrin coated pits!
Comments on Endocytosis into coated vesicles:
 Clathrin and receptors are typically recycled
back to the PM!
– Clathrin has a triskelion-like shape!
– Provides structure to pit and attachment point for
intracellular scaffolding
 Endocytotic vesicles may fuse with lysosomes to
modify/digest vesicle contents!
– Lysosomes are rich in acids and digestive enzymes
 Contents in lysosome removed by diffusion,
remnants removed by exocytosis!
 Many bacteria, protozoan paratites and viral
particles get access to a cell by locking to PM
receptors!
 Drugs may prevent of docking/cell infection!