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BIOL 2021 Lecture Notes - Lecture 11: Cholesteryl Ester, Ldl Receptor, Cell Surface Receptor

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School
York University
Department
Biology
Course
BIOL 2021
Professor
Patricia Lakin- Thomas

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Feb 8th (Lecture 10)
• Fig 13-51 low density lipoprotein (LDL)
o Holds cholesterol, made in the liver.
o Transported to cells in bloodstream as esters in lipid-protein particles.
o Most cholesterol is transported in the blood as cholesteryl esters in the
form of lipid–protein particles known as low-density lipoproteins (LDLs).
• Fig 13-52 endocytosis of LDL
o LDL receptors on cells bind to adaptor proteins, endocytosis in coated
pits. Most cholesterol is transported in the blood as low-density
lipoproteins (LDLs). When a cell needs cholesterol for membrane
synthesis, it makes transmembrane receptor proteins for LDL and inserts
them into its plasma membrane. Once in the plasma membrane, the LDL
receptors diffuse until they associate with clathrin-coated pits that are in
the process of forming. There, an endocytosis signal in the cytoplasmic tail
of the LDL receptors binds the membrane-bound adaptor protein.
o Atherosclerosis = cholesterol deposits, coat artery walls because
receptors aren’t made, or mutant receptors aren’t made. Many animal
cells take up cholesterol through receptor-mediated endocytosis and, in
this way, acquire most of the cholesterol they require to make new
membrane. If the uptake is blocked, cholesterol accumulates in the blood
and can contribute to the formation in blood vessel (artery) walls of
atherosclerotic plaques.
o After endocytosis, coated vesicle uncoats, fuses with endosome →
lysosome, low PH causes LDL release from receptor, hydrolysis to free
cholesterol.
o Since coated pits constantly pinch off to form coated vesicles, any LDL
particles bound to LDL receptors in the coated pits are rapidly internalized
in coated vesicles. After shedding their clathrin coats, the vesicles deliver
their contents to early endosomes. Once the LDL and LDL receptors
encounter the low pH in early endosomes, LDL is released from its
receptor and is delivered via late endosomes to lysosomes. There, the
cholesterol is released, which is now available to the cell for new
membrane synthesis (Movie 13.3). If too much free cholesterol
accumulates in a cell, the cell shuts off both its own cholesterol synthesis
and the synthesis of LDL receptors, so that it ceases both to make or to
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Document Summary

Most cholesterol is transported in the blood as low-density lipoproteins (ldls). When a cell needs cholesterol for membrane synthesis, it makes transmembrane receptor proteins for ldl and inserts them into its plasma membrane. Once in the plasma membrane, the ldl receptors diffuse until they associate with clathrin-coated pits that are in the process of forming. There, an endocytosis signal in the cytoplasmic tail of the ldl receptors binds the membrane-bound adaptor protein: atherosclerosis = cholesterol deposits, coat artery walls because receptors aren"t made, or mutant receptors aren"t made. Many animal cells take up cholesterol through receptor-mediated endocytosis and, in this way, acquire most of the cholesterol they require to make new membrane. After shedding their clathrin coats, the vesicles deliver their contents to early endosomes. Once the ldl and ldl receptors encounter the low ph in early endosomes, ldl is released from its receptor and is delivered via late endosomes to lysosomes.

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Related Questions

Cholesterol is transported in the bloodstream in lipoproteinparticles. There are several classes of lipoprotein particles, butone of the most important classes is called Low-densitylipoproteins (LDL). LDL particles are composed of a single moleculeof a large protein called apolipoprotein, as well as thousands ofcholesterols molecules and phospholipids. Part of theapolipoprotein forms the surface of the particles and faces theaqueous phase, while other parts face the hydrophobic interior ofthe particle where they interact with cholesterol and thehydrophobic tails of the phospholipids. When cells need additionalcholesterol, they produce a receptor protein on the surface oftheir plasma membrane that binds to the apolipoprotein andinitiates the uptake of LDL particles into the cell via a processcalled endocytosis.

1. What is the likely reason that LDL particles are used totransport cholesterol in the blood stream?

a. Cholesterol in LDL particles easily inserts into lipidbilayers

b. Cholesterol id largely insoluble in aqueous solutions

c. Cholesterol is synthesized within LDL particles

d. LDL particles can form lipid rafts in the lipid bilayer

2. What is the most likely location of phospholipids in LDLparticles?

a. Bound to the hydrophilic domain of apolipoprotein

b. In the lipid bilayer that surrounds LDL particles

c. On the surface interacting with the aqueous environment aswell as interacting with the hydrophobic core of the particle

d. Within the hydrophobic core of the particle

3. What best describes the class of protein that apolipoproteinbelongs to?

a. Amphipathic proteins

b. Cell surface proteins

c. Membrane associated protein

d. Multipass membrane proteins

4. What kind of molecule on the surface of the cell would bemost likely to serve as a receptor for LDL particles?

a. a cholesterol binding protein

b. a glycolipid

c. a phospholipid

d. trans membrane protein

5. What conditions would be most likely to trigger increaseduptake of LDL particles by cells?

a. increased glycolipid synthesis

b. increased plasma membrane growth

c. increased protein secretion

d. increase protein synthesis

True or False? True False
1. Proteins rapidly pass artificial membrane (liposome).--------------------------------------------------------------------------------------( ) ( )
2. Amphiphatic detergent such as SDS spontaneously forms bilayer inwater. ------------------------------------------------------------( ) ( )
3. Cholesterol does have a hydrophilic head and hydrophobic tail.-------------------------------------------------------------------------( ) ( )
4. Fat molecules are one of the major components of the plasmamembrane.------------------------------------------------------------- ( ) ()
5. Phospholipid molecules such as phosphatidylcholine spontaneouslyform bilayer. ----------------------------------------------------( ) ( )
6. Flippase facilitates lateral movement of phospholipids withinthe plane of the membrane.----------------------------------------- ( ) ( )
7. Glycolipids make bilayer less permeable to small water solublemolecules.----------------------------------------------------------- ( ) ()
8. Membrane inner leaflet is enriched with phosphatidylcholine,Sphingomyelin, and Glycolipid. -----------------------------------( ) ( )
9. Plasma membrane proteins can have an enzyme activity.--------------------------------------------------------------------------------( ) ( )
10. A single pass membrane protein must have an amphiphatic alphahelix.-------------------------------------------------------------- ( )( )
11. Plasma membrane proteins can be linked to a lipid molecule atthe outer leaflet of the plasma membrane. --------------------- ( )( )
12. The lateral motility of membrane proteins can be restricted bytight junctions.------------------------------------------------------ ( ) ()
13. Channel proteins have specific binding sites for ions and thusslower than carrier proteins.--------------------------------------- ( ) ( )
14. An antiport would function as a symport if its orientation inthe membrane were reversed. ---------------------------------------( ) ( )
15. A transmembrane pore can be formed by multiple amphipathicalpha helices. ----------------------------------------- ( ) ()
16. Porin proteins form water-filled channels in the outer membraneof a bacterium and are mostly composed of beta sheets. ---- ( ) ()
17. Glucose uniporters localize at the apical side of theintestinal epithelium.------------------------------------------------------------ ( ) ()
18. GAP junction is a selective pore for anions.-----------------------------------------------------------------------------------------------( ) ( )
19. A voltage-gated Na+ channel adopts only two conformationstates: open and closed.----------------------------------------------- ( ) ( )
20. Voltage gated K+ channel opens faster than the Voltage gatedNa+ channels.-------------------------------------------------------- ( ) ()
21. Opening of chloride channel at the synapse will help to fire anaction potential.------------------------------------------------------ ( ) ()
22. The nuclear pore complex forms a gate through which moleculespass the nucleus uni-directionally. -------------------- ( ) ()
23. A completely folded protein is imported into a mitochondrionthrough a large non-selective pore.--------------------------------- ( ) ( )
24. ER signal sequence contains multiple lysine and arginineresidues.----------------------------------------------------------------------( ) ( )
25. The plasma membrane is a sorting station of inward endocyticpathway.---------------------------------------------------------------- () ( )
26. The trans Golgi functions as a sorting station of outwardsecretory pathway.----------------------------------------------------------- ( ) ()
27. Vesicles budding from ER are coated with Clathrin.----------------------------------------------------------------------------------------( ) ( )
28. RabGTPases and tethering proteins are the major specificitydeterminant of vesicle transport system. --------------------------( ) ( )
29. v-SNARE proteins are one of the tethering proteins.------------------------------------------------------------------------------------( ) ( )
30. In secretory cells, the constitutive and regulatory pathways ofexocytosis diverge at the cis Golgi network. ------------------ ( )( )
31. Many proteins are posttranslationally glycosylated at tyrosineresidues in the ER.------------------------------------------------- ( ) ( )
32. Cells import LDL molecules exclusively through pinocytosis.-------------------------------------------------------------------------( ) ( )
33. Cells recycle LDL receptors from lysosome to the plasmamembrane.----------------------------------------------------------------- () ( )
34. Phagosomes fuse with late endosome.------------------------------------------------------------------------------------------------------( ) ( )
35. Small vesicles from ER near the plasma membrane can fuse withthe plasma membrane upon bypassing Golgi apparatus. -- ( ) ()
36. If a Sec mutant showed an accumulation of newly synthesizedproteins at ER,
then the Sec gene is likely a component of vesicle-buddingmachinery of trans-Golgi network.------------------------------------ ( ) ( )
37. A signal recognition particle is a single pass trans-membraneprotein of the ER membrane.---------------------------------------- ( ) ( )
38. Typical animals cells display higher levels of intracellularsodium than extracellular compartments.------------------------------ ( ) ( )
39. Typical animals cells display higher levels of intracellularchloride than extracellular compartments.----------------------------- ( ) ( )
40. The Na-K Pump is a GTPase that can adopt active and inactiveconformational states.----------------------------------------------- ( ) ( )
1. Phospholipase
C-­-ß
produces
phosphatidylinositol
3,4,5-­-trisphosphate
and
diacylglycerol.
(
)
(
)
2. PDGF
activates
GPCR.
-­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­----­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­-
(
)
(
)
3. Rho
is
an
example
of
heterotrimeric
G
proteins.
-­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­----­--­--­--­--­--­-
(
)
(
)
4. All
members
of
the
G
protein
coupled
receptors
interact
with
small
GTPase
Ras.
-­--­--­--­--­--­--­--­--­--­-
(
)
(
)
5. Adrenaline
is
an
example
of
the
ligands
for
the
RPTK
family.
-­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­-
(
)
(
)
6. Ras
GEF
activates
RPTK.
-­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­----­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­-
(
)
(
)
7. PH
domain
containing
proteins
bind
to
activated
EGFR.
-­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­-
(
)
(
)
8. Ligands
for
GPCR
proteins
induce
dimerization
of
the
receptor.
-­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­-
(
)
(
)
9. Grb2
is
an
adaptor
protein
that
binds
to
a
phospho-­-tyrosine
residue
of
activated
RPTK
through
a
PH
domain.
-­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­----­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­-
(
)
(
)
10. When
a
cell
is
expressing
a
large
number
of
dominant
negative
EGFR
proteins,
an
introduction
of
a
constitutively
active
Ras
mutant
will
allow
EGF
signaling.
-­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­-
(
)
(
)
11. PI3K
generates
phosphatidylinositol
3,4,5-­-trisphosphate
from
IP3.
-­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­-
(
)
(
)
12. Calcium
inhibits
PKC.
-­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­----­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­-
(
)
(
)
13. cAMP
activates
PKA.
-­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­----­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­-
(
)
(
)
14. The
MAP
kinase
ERK
inhibits
MAP
kinase
kinases.
-­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­----­--­-
(
)
(
)
15. cAMP
is
an
example
of
a
first
messenger.
-­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­----­--­--­--­--­--­--­--­--­--­--­--­--­--­--­-
(
)
(
)
16. All
7-­-Transmembrane
receptors
are
G
Protein
Coupled
Receptors.
-­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­--­-
(
)
(
)
17. Both
Ga
and
Gß
subunits
of
the
heterotrimeric
G
protein
can
mediate
GPCR
signaling.
-­--­--­-
(
)
(
)
18. Both
Ga
and
Gß
subunits
of
the
heterotrimeric
G
protein
have
GTPase
activity.
-­--­--­--­--­--­--­--­--­--­--­--­-
(
)
(
)
19. The
Gas
subunit
of
the
heterotrimeric
G
protein
suppresses
the
function
of
Adenylyl
cylase.
(
)
(

The vesicles that transport materials from donor membranes to acceptor membranes include:

1.

COP-II coated vesicles
2.

COP-III coated vesicles
3.

COP-I coated vesicles
4.

Clathrin coated vesicles

2.5 points

QUESTION 11

During skeletal muscle contraction, the roles of ATP include:

1.

ATP is not required for forming the crossbridges between myosin and actin filaments.
2.

ATP is utilized as a structural linker to mediate the interaction between myosin and actin filaments
3.

Hydrolysis of ATP provides energy for myosin head to move along actin filaments and the binding of ATP to myosin head allows the detachment of myosin fromactin filaments.
4.

ATP binds to actin filaments to drive the power stroke of myosin head.

2.5 points

QUESTION 12

One of the functions of smooth endoplasmic reticulum is

1.

Synthesizing steroid hormone in the endocrine cells of the gonad and adrenal cortex
2.

Serves as the starting point of the biosynthetic pathway
3.

Synthesizing secretory proteins
4.

Degrading cell debris

2.5 points

QUESTION 13

The function of COP-II coated vesicles is mainly:

1.

Transporting materials from endosomes to Golgi complex
2.

Moving materials from the ER to the ERGIC and Golgi complex.
3.

Transporting materials from Golgi complex back to endoplasmic reticulum.
4.

Involved in receptor-mediated endocytosis.

2.5 points

QUESTION 14

Which of the following processes is completed in rough endoplasmic reticulum?

1.

Chaperones help misfolded proteins fold correctly.
2.

Proteins that target to nucleus are synthesized in rough endoplasmic reticulum.
3.

O-linked glycosylation occurs in rough endoplasmic reticulum.
4.

Misfolded proteins are destructed in rough endoplamic reticulum.

2.5 points

QUESTION 15

Kinesin is the motor protein that coorporates with microtubules. It has the following functions:

1.

It uses GTP as energy source.
2.

It can hydrolyze ATP and use the energy to drive cargo along microtubules from minus end to plus end.
3.

It has a globular head that can act as GTPase
4.

The tail of kinesin is more diverse and binds to cargo

2.5 points

QUESTION 16

For correct segregation and trafficking, lysosomal proteins are tagged in the cis-Golgi with phosphorylated mannose residues, and then the tagged lysosomal enzymes are recruited to clathrin coated vesicles by mannose 6-phosphate receptors.

True

False

2.5 points

QUESTION 17

The process that specialized cells, such macrophages, engulf relatively large particles is:

1.

Called pinocytosis
2.

Called phagocytosis
3.

Mediated by COP-II coated vesicles
4.

Called autophagy

2.5 points

QUESTION 18

Proteins synthesized on rough endoplasmic reticulum and smooth endoplasmic reticulum are imported co-translationally to their destinations

True

False

2.5 points

QUESTION 19

Treatment of cells with a drug that promotes microtubule disassembly disperses Golgi complex into separate stacks of membrane compartments, suggesting that:

1.

Golgi complex is made of microtubules.
2.

Microtubules are important for the organization of Golgi complex.
3.

Microtubules are transported into Golgi complex
4.

Golgi complex is composed of tubulin proteins

2.5 points

QUESTION 20

Which of the following is correct about signal sequence of a secretory protein?

1.

It is an “address codes” for protein trafficking pathways
2.

It is usually located at the C-terminus.
3.

It targets the ribosome and the protein that is being synthesized to endoplasmic reticulum.
4.

It is removed in Golgi complex.