Exam 2 Material Flashcards
(94 cards)
1
Q
What are some functions of the cell membrane?
A
- A barrier to prevent escape/entry
- Separation of intracellular compartments from other aspects of the cell
- Receive signals from ECM
-Import/Export
-Expand for growth/Facilitate movement
2
Q
What is the word used to describe phospholipids and what does it mean?
A
Amphipathic- has both hydrophilic/hydrophobic qualities
3
Q
What are the different portions of phospholipids? IN ORDER
A
- Choline or Serine (Polar head group)
- phosphate group
- Glycerol (3C sugar)
- Two long hydrocarbon tails (fatty acid)
4
Q
What is the difference between phosphatidylserine and phosphatidyl choline?
A
The polar head group on the phospholipid- one is serine and the other is choline (more common)
5
Q
What is the difference between saturated and unsaturated fatty acids?
A
Saturated fatty acids: All C-C bonds are fully hydrogenated
Unsaturated: C=C bonds, so some hydrogens are lacking
6
Q
Where are phospholipids manufactured?
A
The SMOOTH ER
7
Q
On which side of the Smooth ER are phospholipids incorporated?
A
On the CYTOSOLIC side
8
Q
What does the enzyme Scramblase do?
A
Causes the symmetric growth of the growing membrane by scrambling phospholipids during production
9
Q
Describe Membrane Assembly (likely phosphatidylcholine)
A
- Within the Smooth ER
- Phospholipids can only be incorporated on the cytosolic side of the ER
- Enzyme scramblase scrambles phospholipids from one monolayer to other, resulting in symmetric growth of nascent membrane
- Growing ER membranes bud off to be transported to other membranes through the Golgi, such as the plasma membrane
10
Q
What does the enzyme Flippase do?
A
It is an ATP dependent enzyme that makes sure that phosphatidylserine faces the cytoplasmic side
11
Q
What does the presence of phosphatidylserine on the outside of a cell mean and Why?
A
It means that the cell is dying, as Flippase is inactivated due to the lack of ATP. SO, scramblase comes in and flips the phosphatidylserine to face the exoplasmic face of the plasma membrane
12
Q
What is the difference between Passive Transporters and Active Transporters?
A
Passive transporters move solute along a concentration gradient, while active transporters require energy.
13
Q
What kind of molecules can pass through membranes by simple diffusion, and give an example
A
Lipophilic molecules such as hormones (cortisol, sex hormones)
14
Q
Describe Transporter-Mediated Transport, and is it passive or active transport?
A
The transporter binds to the solute molecule, and changes shape to allow entry into the cell. This is an example of passive transport
15
Q
Describe the movement of Calcium (2+) from cytosol to the lumen of the sarcoplasmic reticulum
What kind of transport is this?
A
-Ca from the cytosol enters the binding site
- ATP binds the cytosolic side and phosphorylates an aspartic acid
- Conformation change pushes Ca to the sarcoplasmic reticulum (smooth ER in muscle)
This is Active Transport
16
Q
What are the relative concentrations of Ca (2+) in the smooth ER of the muscle (what it that called) and in the cytoplasm?
A
High Ca in the sarcoplasmic reticulum
Low Ca in the cytoplasm
17
Q
Describe the Sodium Potassium Pump
A
1) Unbound protein
2) Sodium binds (3x)
3) Shape change
4) Release of Na+
5) Unbound protein
6) Potassium binds (2x)
7) Shape change
8) Release of potassium
18
Q
What does the sodium potassium pump do for the cell?
A
-Maintenance of Electrical Potential across the plasma membrane
- High concentration of extracellular Na
- High conc of intracellular K
19
Q
What two forces occur with potassium in the Sodium-Potassium pump and what is the result?
A
1) K+ specifically wants to move out following the concentration gradient
2) K+ charge wants to move in according to electrochemical gradient
Result: Potassium partially follows concentration gradient via leak channels but cannot come to equilibrium due to positive charge outside the cell
20
Q
What channel responds to membrane depolarization?
A
Voltage-gated ion channels
21
Q
What channel responds to presence of ligand?
A
Ligand-gates ion channels
22
Q
What channel responds to deformation of plasma membrane (stress)?
A
Mechanically-gated ion channels
23
Q
What does an AMPA Glutamate Receptor do? (Neurons)
A
-Binds glutamate and AMPA
-Ligand-gated ion channel
-CNS major excitatory Neuron
(in neurons)
24
Q
What do the Voltage-gated Sodium Channels do in Neurons?
A
Via Axon Polarization, the Na(2+) channels open, and down the axon, the voltage flips left to right.
25
What does the Calcium Channel do in Neurons?
-Intra-cellular Ca--> vesicle fusion
-Neurotransmitters Enter the Synaptic Cleft
- Activation of Downstream Neuron
Make sure you know how Neurons are excited by Neurotransmitters!
26
Describe how Voltage-Gated Sodium channels quickly inactivate.
-Membrane depolarization opens the voltage-gated Na+ channels
-Opens briefly for a small rush
- To prevent permanent neuron stimulus, the channel inactivates
27
Describe how Voltage-Gated Potassium Channels (and Leak Channels) work
-Local rise in intracellular sodium ion (Na+) triggers voltage gated K channels to open
(which are NOT leak channels)
This allows K+ to quickly exit the cell along it's concentration gradient.
Sodium Potassium pump works to reestablish the polarized state of the cell
28
Explain how Bacteriorhodopsin works
-During periods of daylight, retinal absorbs a photon which causes a shape change in the core of the protein
-This allows a proton to be released from retinal to extracellular space
- This protein in retinal is replenished from the cytosol
-Drives proton gradient and ATP production in bacteria during the day
29
Explain the application of Bacteriorhodopsin/Optogenetics in mice
-A mouse gets a deep brain injection of a retrovirus that carries the recombinant gene for the light-sensitive proton pump
-Gets a fiber optic cable in brain
-Light activates rBR, which causes neurons that express AgRP (Agouti-related protein) to be stimulated.
(The specific example in class showed that the presence of light caused the mouse to go eat food/be aggressive)
30
What is protein sorting?
The process through which proteins and enzymes are trafficked from the cytoplasm to the correct compartment within the cell
31
What happens when a protein's signal sequence is genetically altered?
Proteins can be retargeted to different compartments within the cell
32
What happens to proteins who do not have a signal sequence?
They remain in the cytosol
33
Do minor signal sequence changes dramatically change how they work?
No, they do not
X-Y-Z-A
X-Y-Z-B (would still work)
34
What are the three ways that proteins are trafficked?
1) Transport through nuclear pores
2) Transport across membrane
3) Transport by vesicle
35
Describe how nuclear proteins get imported through Nuclear Pores
-Nuclear Import receptors (Importins) bind the Nuclear Localization Sequence (NLS) of a nuclear protein
-The protein-receptor complex interrupts the disordered tangle of nuclear pore proteins that fill the center of the pore
-This allows for local passageway for entry
36
Describe how GTP is used in Nuclear Import
-In order to move the nuclear import receptor back into the cytosol, the protein Ran is used
-GTP binds to Ran, and the GTP displaces the nuclear protein and steers the complex back into the cytosol
-GTP is then hydrolyzed to GDP, which causes the Ran to dissociate
37
Briefly describe the Ran cycle
Ran-GTP binds to nuclear transport factor 2, and is taken back into the nucleus for GTP exchange
38
Describe how proteins are transported into the mitochondria/chloroplasts
- N-terminal Signal Sequence binds translocators on the outer and inner membranes
- Chaperone Proteins in the organelle assist in transporting and refolding on entry (fold into correct shape)
-Signal sequence is proteolytically cleaved
Note: protein folding = lowest energy state
39
What enzyme is responsible for cleaving the signal sequence of a protein within the mitochondria?
Signal Peptidase
40
What are the two pathways in which proteins are sorted into the peroxisome?
1. Cytosolic proteins containing the peroxisome signal sequence are selectively targeted to peroxisomes via protein translocators
2. Other peroxisomal proteins are translated into the endoplasmic reticulum, which are then budded off as small vesicles that fuse to peroxisomes
41
Describe the process that results in many proteins being produces from mRNA
-Each mRNA recruits a ribosome to the 5’ end to initiate translation
-As one ribosome processes the mRNA, another ribosome can begin translation
-This results in a polyribosome
42
What are the two kinds of proteins that are manufactured in the ER? What are their fates?
1. Water-soluble protein that are completely translocated across the ER membrane
Fate: These are either secreted extracellularly or target to another organelle in the endomembrane system
2. Prospective transmembrane proteins that are only partly translocated across the ER membrane
Fate: These are destined to remain transmembrane proteins in an organelle or plasma membrane
43
What is a signal recognition particle, where is it and what does it do?
Located on transmembrane proteins, they contain a signal recognition sequence that stalls ribosomal translation
44
Describe how proteins with signal recognition sequences are brought into the ER
-Transmembrane proteins contain a signal recognition sequence that binds the Signal Recognition Particle (SRP), which stalls ribosomal translation
-Stalled ribosomes attach to the ER membrane
-This signal targets the translated protein for translation into the ER
-This creates distinct regions of “Rough Endoplasmic Reticulum”, where protein translation continues when bound to the ER membrane
45
What three components are needed for the movement of a protein into the ER?
1. Signal recognition particle (SRP)
2. SRP
3. ER protein translocator
46
After signal peptidase cleaves the signal recognition sequence, what happens next?
The translated protein is released from the ER membrane and can fold in the ER lumen
47
What happens to TRANSMEMBRANE proteins with N-TERMINAL signal recognition sequences?
- For transmembrane proteins, a signal recognition sequence initiates translation through the ER membrane
- A second hydrophobic stop transfer sequence prevents further protein translocation
- Protein translation continues in the cytosol
48
What happens to TRANSMEMBRANE proteins with INTERNAL signal recognition sequences?
- If the Signal Recognition Sequence is internal (rather than N-terminal) the growing peptide is threaded through the ER membrane
-Translation into the ER lumen continues until a second hydrophobic sequence halts threading the into ER lumen
-Internal recognition sequences are NOT cleaved by signal peptidase
49
What does signal peptidase cleave (specifically)?
Only N-terminal Signal Sequences
50
What happens when there is a second signal sequence on a protein?
After signal peptidase cleaves the N-terminal signal sequence, the second signal sequence is retained in the protein translocator and translation continues
51
Where are proteins that are translated in the ER lumen destined to go?
They will go to other organelles or will be secreted
52
Where will proteins that were originally transmembrane proteins in the ER end up?
They can either be transmembrane proteins on organelles or the plasma membrane
53
If a terminus (N) is translated in the cytosol, where where it be after vesicle transport?
It will remain in the cytosol
54
If a terminus (N) is translated in the Lumen, where where it be after vesicle transport?
Not the cytosol (probably in the ECM)
55
What are transport signals?
regions of the trafficked polypeptide that bind to transmembrane cargo receptors on the ER membrane
56
Describe Vesicle Formation
- Adaptins (effector proteins) cluster similar cargo receptors together in a nascent vesicle and associate with specific Rab proteins
-Cargo receptor/adaptin complex binds clathrin (coat protein)
-Clathrin provides strain on the budding membrane ,causing vesicle formation
-Dynamin pinches the bud
off the ER
57
What do the Rab proteins on vesicles do?
They are recognized by tethering proteins on the target membrane – ensures targeting to correct membrane or organelle
58
What are t-snares?
Proteins that connect with v- snares to fuse vesicle to target membrane
59
What are V-snares?
They connect with t-snares to bring the vesicle to the target membrane, so the bilayers can fuse.
60
What are tethering proteins?
They bring in the vesicle so that the V-snares and the T-snares can connect
61
What do the following do?
-Cargo receptors
-Adaptins
-Clatherin
-Dynamin
Cargo receptors- Bind clathrin and adaptin as well as the target cargo molecule.
Adaptins- Gather and group similar cargo receptors in a vesicle with specific Rab proteins.
Clathrin- Causes the vesicle to form by straining the budding membrane.
Dynamin- Pinches the vesicle formation bud off of the ER.
62
Describe how vesicles fuse to target membranes?
1) Rab proteins on vesicles are recognized by tethering proteins on the target membrane – ensures targeting to correct membrane or organelle
2) Additional recognition is provided by SNARE transmembrane proteins – specific v-SNAREs (vesicle) bind to specific t-SNAREs (target)
3)Tethering proteins bring v-snares close to the t-snares
4) The v and t snares wind together to that the lipid bilayers fuse
63
Describe how proteins are modified in the ER and a golgi and provide a real-world example
-Disulfide bonds are formed in the ER (the cytosol contains a high concentration of reduced glutathione) – typically on soluble proteins
-Oligosaccharides attached to the lipid dolichol are transferred to specific Asparagine residues on proteins in the ER and Golgi – typically transmembrane proteins
Blood types A,B,AB, O all comes from different sugar modifications attached to oligosaccharide receptor proteins
64
Describe the role that Chaperone proteins play in the ER
- Chaperone proteins bind to misfolded proteins and multimeric proteins that do not bind together properly
-Chaperone proteins keep peptides separate so that misfolded proteins do not aggregate together in aberrant ways
65
What is proteostasis?
The "okay" balance between folded and misfolded proteins, to where chaperone proteins can handle it
66
Describe the Unfolded Protein Response (UPR)
When misfolded proteins accumulate in the ER, the Unfolded Protein Response (UPR) is triggered
This leads to transcription of more chaperone genes, or in severe events, apoptosis
67
What happens when there is too many misfolded proteins?
The misfolded proteins can "encourage" properly folded proteins to misfold, leading to diseases such as Huntington's and Alzheimers, which is why the UPR/induced apoptosis is so important
68
Describe how proteins are trafficked through the golgi
Proteins enter the cis Golgi network (same side as ER, nucleus)
During the passage through the Golgi, oligosaccharides are further modified through a variety of Golgi enzymes
Proteins exit the trans golgi network
69
What is unregulated exocytosis?
The constitutive release of proteins, no signal needed
70
What is regulated cytosis?
secretes proteins upon activation by an extra-cellular signal
71
What is the difference between phagocytosis and pinocytosis?
Phagocytosis is the engulfment of large particles
Pinocytosis is the indiscriminate engulfment of extracellular molecules and fluid, often for nutrients or biomolecules
72
Unless there is a signal sequence, where is all translation initiated?
In the cytoplasm
73
For a protein to be excreted via exocytosis, where must it come from?
The ER
74
What process describes the transport of Cholesterol and other extracellular molecules within the cell
Receptor-mediated Endocytosis
75
Describe how Receptor-mediated endocytosis moves cholesterol around the cell
-Low-density lipoprotein carries cholesterol
- The LDL receptor binds to LDL for endocytosis and recycling of cholesterol
- Results in selective concentration of particular macromolecules in particular cells that express the receptor
76
What are the three fates of vesicles traveling through the gut mucosal cell?
- recycling back to apical plasma membrane
- degradation into lysosome
- transcytosis to another membrane of the cell
77
What is the role of lysosomes?
Principal sites of intracellular digestion
78
How is the lumen of the lysosome acidified?
ATP-dependent proton pump
79
What happens to the digested contents of the lysosome?
They are exported to the cytosol through metabolite transporters
80
What are the four ways that cells receive information
-endocrine
-paracrine
-synaptic
-contact-dependent
81
Briefly describe what molecules are transported in the Endocrine system and how
Hormones produced in endocrine cells are secreted into the bloodstream and distributed widely:
-Adrenaline
-Cortisol
-Insulin
-Thyroid Hormone
-Estradiol/Testosterone
82
Briefly describe what molecules are transported in the Paracrine system and how
Paracrine signals are secreted by cells locally into the extra-cellular matrix to signal to neighboring cells:
-Epidermal Growth Factor (EFG)
-Platelet-derived Growth Factor (PDGF)
-Nerve Growth Factor (NGF)
-Histamine
-Nitrous Oxide (NO)
83
Briefly describe what molecules are transported in the Neuronal system and how
Neuronal signals are transmitted electrically down the axon, causing the release of neurotransmitters into the synapse to signal to a single target cell (dendrites)
-Glutamate
-Acetylcholine
-𝛄-Aminobutyric acid (GABA)
84
Briefly describe what molecules are transported via Contact-Dependence and how
Cell surface bound signal molecule binds a receptor protein on a target cell- contact dependent
-Delta/Notch Signaling
-Cellular Adhesion Molecules
85
Describe how Cortisol regulates transcription
A conformational change activates the receptor protein
Activated receptor-protein complex moves to nucleus
Activates complex binds to regulatory region of target gene and activates transcription
86
Describe how Estradiol causes a change in gene expression
Production of Estrogen (estradiol) by the ovaries moves to different cells in the blood
Estrogen binds to the Estradiol Receptor to make it an active transcription factor. The transcription factor binds to the Estrogen Response Element (ERE) in DNA, causing normal changes in cellular physiology to make mammary tissue and other sex hormones
87
Rank the different cell signaling from the farthest distance to the closest
Farthest- Endocrine
Paracrine
Synaptic
Closest- Contact- Dependent
88
Describe how Extracellular signaling can change cell behavior
Receptor proteins activate one ore more intracellular signaling pathways
Can be proteins or small messenger molecules
Signaling molecules interact with specific effector proteins which cause a change in cell behavior
89
Describe how Acetylcholine affects Heart pacemakers, salivary and skeletal muscle cells
When acetylcholine binds to receptor proteins on the membrane it:
Decreases rate of firing (heartbeat)
Secretion (salivary gland)
Contraction (skeletal muscle cell)
90
Describe how acetylcholine activates Nitric Oxide to generate soluble nitrous oxide, which causes the muscle relaxes.
When acetylcholine binds to the receptor protein, it activates NO synthase, which breaks down nitroglycerine from arginine, which is immediately converted to NO.
The NO rapidly diffuses across membranes to bind to guanylyl cyclase. With this binding, along with the conversion of GTP to cyclic GMP, the muscle relaxes.
91
What are the three Cell-Surface receptors?
1. Ion-channel coupled
2. G-protein-coupled Receptors
3. Enzyme-coupled Receptors
92
What happens with Ion-channel coupled receptors and what is an example of one?
Ligand (signal molecule) binding causes a change in the conformation of the receptor to allow ions to pass through
Example: Activation of AMPA Receptor By Glutamate or AMPA Allows Calcium to Enter Cells
93
What happens with G-protein coupled Receptors (overview) and what are examples of some?
G-protein-coupled receptors undergo a conformational change when bound to ligand
This activates the intracellular G-protein which transduces the signal to a membrane-bound enzyme
Example: sight, smell (???)
94
Describe how the three subunits of G-proteins are binding signaling molecules
-G-proteins are composed of 𝛂-, 𝛃-, and 𝛄- subunits
-When a signaling molecule binds to the G-protein-coupled receptor, it exchanges the GDP for GTP on the 𝛂 subunit
-This frees the activated 𝛂- and 𝛃𝛄-subunits
-The activated 𝛂- and 𝛃𝛄-subunit can activate downstream effector proteins
