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What generates action potentials in excitable cells?
Voltage-gated cation channels
Does action potential amplitude decrease as it moves down the axon?
No — it remains constant
During N-linked glycosylation, what happens immediately after the first seven sugar residues are assembled on the dolichol carrier? (Lec 11 slides 12-19 and Lec 12 slide 11)
The dolichol-linked oligosaccharide flips to the luminal side of the ER membrane
What increases the speed and efficiency of action potential propagation?
Myelination
What cells create myelin in the PNS?
Schwann cells
What type of signaling occurs at most neuronal synapses? (Lec 13B&C slide 7)
Chemical neurotransmission
What triggers neurotransmitter release at the presynaptic terminal? (Lec 13A slides 19-20)
Ca²⁺ entry through voltage-gated Ca²⁺ channels
What is the primary role of the Signal Recognition Particle (SRP) in eukaryotes?
It recognizes ER signal sequences, temporarily pauses translation, and targets the ribosome-nascent protein complex to the ER membrane.
What determines whether a synapse is excitatory or inhibitory? (Lec 13B&C slide 5 and Lec 14 slide 6-7)
The ligand-gated ion channels on the postsynaptic membrane
What type of receptor is the nicotinic acetylcholine receptor? (lec 13 slide 16-17 & Lec 14 slide 6-7)
Excitatory ionotropic transmitter-gated cation channel
Which subunits bind acetylcholine? (Lec 13B&C slide 17)
Alpha subunits
What is the major fast excitatory neurotransmitter in the vertebrate CNS? (Lec 13B&C slide 5)
Glutamate
What is the major inhibitory neurotransmitter in the vertebrate CNS? (Lec 13B&C slide 5)
GABA (gamma-aminobutyric acid)
Which of the following are the two major cellular responses produced by ionotropic receptors? (Lec 14 slide 7)
A) Changes in gene expression and protein synthesis.
B) Changes in membrane potential and increases in cytosolic Ca²⁺.
C) Activation of G proteins and production of cAMP.
D) Activation of protein kinases and phosphorylation cascades.
B) Changes in membrane potential and increases in cytosolic Ca²⁺.
What (from the choices below) must cells interpret to determine their ultimate fate? Do not write letter in answer.
A) Only the first chemical messenger received
B) Only signals from intracellular receptors
C) Only the concentration of a single neurotransmitter
D) A combination of signaling events
A combination of signaling events
What ion entering through NMDA receptors is required for LTP? (Write the ion name)
Calcium
Which protein acts as the calcium sensor during synaptic vesicle fusion? (Lec 13A slide 19)
Synaptotagmin
What happens following Ca²⁺ influx during the final stages of synaptic vesicle fusion? Lec 13A slides 20-21
A) Complexin binds to SNARE complexes and prevents their completion.
B) Synaptic vesicles are transported back to the Golgi.
C) SNARE proteins are degraded before membrane fusion.
D) SNARE-complex formation is completed and complexin dissociates, permitting fusion.
D) SNARE-complex formation is completed and complexin dissociates, permitting fusion.
Why can acetylcholine produce different responses in different target cells?
Lec 13B&C
slides 14-16 and 18-21
Target cells express different receptors and signaling machinery.
What activates mechanically-gated ion channels?
Physical force or membrane deformation
Which of the following sensory cells use mechanically gated ion channels to detect sound vibrations?
A) Retinal photoreceptor cells
B) Olfactory receptor neurons
C) Auditory hair cells in the cochlea
D) Taste receptor cells
C) Auditory hair cells in the cochlea
What structure in hair cells communicates mechanical force?
Stereocilia
Where does all protein synthesis occur in eukaryotic cells? (Lec 9 slide 2)
In the cytosol, except for proteins encoded by mitochondria and chloroplasts.
Why can't proteins diffuse across membranes?
The lipid bilayer is impermeable to proteins.
What directs proteins to the correct compartment?
Signal sequences built into the primary structure of the nascent polypeptide.
When are signal sequences typically removed? (Lec 9 slide 7)
After transport into the target compartment.
What are the three major strategies for protein sorting?
Gated transport, transmembrane transport, and vesicle transport
Where does vesicular transport begin?
Endoplasmic reticulum
What does "topologically related compartments" mean?
Compartments that can exchange proteins without those proteins crossing a lipid bilayer.
What determines whether a protein stays luminal or cytosolic as it moves through the endomembrane system?
Its orientation during initial insertion into the ER.
What are signal sequences?
Short stretches of amino acids that direct proteins to specific compartments.
What is a signal patch?
A 3D arrangement of amino acids formed after folding that serves as a sorting signal.
What is the general structure of an ER signal sequence?
A stretch of 8+ consecutive nonpolar amino acids (NPAA).
Where can ER signal sequences be located?
At the N-terminus or internally, with internal NPAA sequences often becoming transmembrane domains.
Where are mitochondrial signals located?
At the N-terminus of the polypeptide.
What is unique about mitochondrial signal sequences?
They form an asymmetrically charged α-helix.
How is targeting to specific mitochondrial subcompartments achieved?
By additional internal sorting sequences within the polypeptide.
What is the peroxisome targeting sequence?
SKL (Ser-Lys-Leu) near the C-terminus
What does the KDEL sequence do?
Retrieves escaped ER-resident proteins from the Golgi back to the ER.
Where are NLS sequences located?
Anywhere within the folded protein, including internal regions.
What is the general composition of an NLS? (Lec 9 slide 24)
Two prolines, five basic amino acids, and at least one nonpolar amino acid.
Are NLS sequences always exposed? (Lec 9 slide 24)
No, their exposure may depend on modifications such as phosphorylation.
What size molecules pass freely through NPCs? (Lec 9 slides 30 & 34) Molecules smaller than ________ (write the numerical value and the unit)
5 kDa
How many proteins make up the NPC? (Lec 9 slides 30 & 34)
About 30 different proteins.
Do most proteins require assistance to cross the NPC? Why or why not?
Yes — especially proteins larger than 60 kDa.
What proteins escort cargo through the NPC? (Lec 9 slides 36, 38-40)
Nuclear transport receptors (NTRs).
What determines directionality of nuclear transport? Lec 9 slides 40-45
The asymmetric distribution of Ran-GTP in the nucleus and Ran-GDP in the cytosol.
What does Ran-GEF do?
Located in the nucleus — promotes exchange of Ran-bound GDP for GTP.
What does Ran-GAP do?
Located in the cytosol — stimulates hydrolysis of Ran-GTP to Ran-GDP.
What happens when Ran-GTP binds to a nuclear import receptor (NIR)?
The receptor releases its cargo into the nucleus.
What stabilizes cargo binding to a nuclear export receptor (NER)? (Lec 9 slide 43)
Ran-GTP binding to the export receptor.
What powers nuclear transport through nuclear pore complexes (NPCs)?
The Ran-GTPase system
Where is Ran-GTP found? Lec 9 slides 41, 45
In the nucleus.
Where is Ran-GDP found?
In the cytosol.
What is the "default" compartment for synthesized proteins?
Cytosol, unless a sorting signal directs them elsewhere.
What is incorporated into every transported protein?
A sorting signal in the primary structure of the nascent polypeptide.
When are sorting signals often removed?
After transport into the destination compartment.
What state must proteins be in to enter mitochondria?
Unfolded state.
What drives import into the mitochondrial matrix?
H⁺ gradient across the inner membrane, ATP hydrolysis in the cytosol and matrix.
What do mitochondrial targeting sequences form?
An amphipathic α-helix at the N-terminus.
What are the two major types of ER?
Rough ER (ribosomes) and Smooth ER (no ribosomes).
What do internal NPAA sequences usually become?
Transmembrane domains.
What molecule recognizes ER signal sequences?
Signal Recognition Particle (SRP).
What is SRP made of?
Lec 10 slides 29-30
One non-coding RNA + six proteins.
What happens when SRP binds the signal sequence? Lec 10 slides 30, 35-36
Translation is temporarily arrested.
What complex allows proteins to pass into the ER?
Lec 10 slides 37-40
Sec61 translocator complex (aqueous channel).
What acts as the "start transfer signal"?
Lec 10 slides 41-42
The first hydrophobic amino acid sequence.
What cleaves the ER signal sequence after import?
Signal peptidase.
What acts as a "stop transfer signal"? (Lec 10 slide 43)
The second hydrophobic amino acid sequence.
If the first NPAA sequence is at the N-terminus, where is the N-terminus located afterward?
In the ER lumen (extracellular side topologically).
When does translation resume? (Lec 10 slides 35-36)
When SRP binds its receptor and is released.
What determines orientation of internal ER signal sequences?
(Lec 10 slides 45-47)
Charge distribution: (+) side faces cytosol (-) side faces lumen
If the first hydrophobic sequence is internal and positively charged residues flank its N-terminal side, where is the N-terminus?
In the cytosol.
What assists folding of soluble proteins in the ER lumen?
ER chaperones, such as BiP.
Which proteins can leave the ER?
Only properly folded proteins recognized by cargo receptors.
What happens when misfolded proteins accumulate in the ER?
Lec 11 slides 4-5
The Unfolded Protein Response (UPR) is activated
What happens to improperly folded proteins?
They are exported to the cytosol and degraded.
What inserts tail-anchored proteins into the ER membrane?
A special post-translational mechanism independent of co-translational translocation.
Example of a tail-anchored protein?
SNAREs.
How does the professor describe carbohydrate coverage on the cell surface? Don't write letter in answer. (Lec 11 slide 10)
A) A small portion — cells have a "scattering of carbohydrate."
B) A thin portion — cells have a "ring of carbohydrate."
C) A limited portion — cells have a "patchwork of carbohydrate."
D) A large portion — cells are covered in a "jungle of carbohydrate."
A large portion — cells are covered in a "jungle of carbohydrate."
Where are glycoproteins and glycolipids found in the membrane?
On the extracellular leaflet.
What is transferred to Asn residues during N-linked glycosylation?
A 14-residue oligosaccharide from dolichol.
What is the target sequence for N-linked glycosylation?
X= any amino acid except proline
N-X-S/T
What must happen to sugars before they can be added?
They must be activated by attachment to UDP or GDP.
Where are the first 7 sugars added?
In the cytosol.
Where are the last 7 sugars added?
In the ER lumen, after dolichol flips.
What happens to the last two glucose residues?
They are removed during protein folding.
How do oligosaccharides act during trafficking?
They serve as tags marking folding state and Golgi progress.
Where are most membrane lipids synthesized?
In the ER.
How are proteins delivered to compartments of the endomembrane system?
Via transport vesicles.
What are the three major coat protein systems?
Clathrin, COPI, COPII.
What does COP stand for?
COat Protein.
What is the basic clathrin unit?
Lec 11 slides 30-32
A triskelion composed of 3 heavy and 3 light chains.
How many triskelions minimally form a full cage?
36
Can clathrin cages form without membrane?
Yes — they assemble spontaneously in vitro.
How many protein subunits does SRP contain? Write the numerical. (Lec 10 slide 29)
6
What recruits specific cargo into clathrin vesicles?
Lec 11 slide 35
Cargo receptors and adaptins.
What activates adaptins?
Lec 11 slide 35
Binding to specific phosphoinositides (PIs) on the donor membrane.
What do phosphoinositides do?
Lec 11 slide 35
Mark membrane patches for vesicle formation.
What protein constricts the vesicle neck during budding?
Lec 11 slide 35
Dynamin, a GTPase.