Quiz Preparation 02/19 Flashcards
What are the first signs of NMJ formation? (Synaptogenesis II)
Growth cone approaches myotube and makes an unspecialized contact.
How does the basal lamina contribute to NMJ formation after muscle removal? (S2)
It retains synaptic sites, guiding regenerating motor axons to original locations.
What occurs in laminin β2 knockout mice? (S2)
Active zones are poorly developed, and Schwann cells invade the synaptic cleft.
What role does rapsyn play in AChR clustering? (S2)
It anchors AChRs at synaptic sites in response to agrin signaling.
How does synaptic competition refine NMJ innervation? (S2)
Axons compete for control of each muscle fiber, with one axon strengthening while others retract.
What is the role of SNAP-25 in vesicle fusion? (NR)
SNAP-25 contributes two alpha-helices to the SNARE complex, stabilizing vesicle docking.
What is the function of complexin in neurotransmitter release? (NR)
It acts as a clamp to prevent premature fusion of vesicles before Ca2+ influx.
What are pegs, ribs, and beams in active zones? (NR)
Filamentous structures that position vesicles near Ca2+ channels for efficient release.
What is the function of synaptic vesicle recycling? (NR)
Maintains vesicle availability for sustained neurotransmission.
How does Ca2+ binding to synaptotagmin trigger vesicle fusion? (NR)
Ca2+ binding induces a conformational change that promotes SNARE-mediated fusion.
How do RIM proteins contribute to short-term plasticity? (AZ)
They regulate Ca2+ channel function and synaptic vesicle availability.
What role does ELKS play in vesicle docking? (AZ)
It helps maintain the readily releasable pool of vesicles at active zones.
What is the significance of the “T-bar” in Drosophila NMJs? (AZ)
It provides a scaffold for vesicle docking and fusion, ensuring rapid release.
What happens if Munc13 function is disrupted? (AZ)
Vesicle priming is impaired, reducing neurotransmitter release.
How do trans-synaptic adhesion molecules affect active zone alignment? (AZ)
They ensure presynaptic vesicle release sites align with postsynaptic receptors.
What imaging technique revealed the nanostructure of active zones? (AZ)
STED microscopy provided high-resolution images of active zone architecture.
What are the five stages of synaptic development? (S2)
Growth cone approaches myotube
Functional contact is established
Nerve terminal accumulates vesicles and basal lamina forms
Multiple axons converge, then are eliminated
Mature NMJ forms with specialized pre/post-synaptic components
What role does agrin play at the NMJ? (S2)
Agrin induces clustering of acetylcholine receptors (AChRs) at synaptic sites
What is the basal lamina’s role in NMJ formation? (S2)
It contains synaptogenic factors that preserve synaptic organization and promote reinnervation.
What happens to NMJ synaptic sites after denervation? (S2)
Axons regrow and preferentially reinnervate original synaptic sites due to guidance from basal lamina.
How does MuSK contribute to AChR clustering? (S2)
MuSK (muscle-specific tyrosine kinase) is activated by agrin via Lrp4, leading to rapsyn-mediated clustering of AChRs.
What happens in MuSK or agrin mutants? (S2)
AChRs fail to cluster, disrupting NMJ formation.
What are laminin beta2’s roles at the NMJ? (S2)
Laminin beta2 is essential for NMJ maturation; its absence results in impaired active zones and Schwann cell invasion.
How does synaptic elimination occur at the NMJ? (S2)
Initially, multiple axons innervate each muscle fiber, but competition leads to one axon maintaining synaptic contact while others are eliminated.
What is the role of synaptic activity in AChR clustering? (S2)
ACh release disperses AChRs, while agrin stabilizes clusters at synaptic sites.
What is the SNARE complex? (NR)
A three-protein complex (Syntaxin, SNAP-25, Synaptobrevin) that mediates synaptic vesicle fusion with the presynaptic membrane.
What role does synaptotagmin play in neurotransmitter release? (NR)
It acts as a Ca2+ sensor, triggering vesicle fusion upon Ca2+ influx
What are the key steps in the synaptic vesicle cycle? (NR)
Vesicle loading → docking → priming → fusion → endocytosis → recycling.
How does Ca2+ influx contribute to vesicle fusion? (NR)
Voltage-gated Ca2+ channels near the active zone allow localized Ca2+ entry, triggering SNARE-mediated vesicle fusion.
What are the three mechanisms of synaptic vesicle endocytosis? (NR)
Kiss-and-run: Fast, minimal membrane fusion.
Clathrin-mediated: Slower, uses coated pits.
Bulk retrieval: Large-scale endocytosis during high activity.
How do botulinum and tetanus toxins affect neurotransmitter release? (NR)
They cleave SNARE proteins, preventing synaptic vesicle fusion and neurotransmitter release.
What is the role of Munc13 in synaptic vesicle priming? (NR)
Munc13 helps convert docked vesicles into a fusion-ready state by interacting with SNARE proteins.
What is synaptic plasticity? (NR)
The ability of synapses to strengthen or weaken over time in response to activity.
What are the four major functions of the active zone? (AZ)
Docking and priming vesicles
Recruiting and stabilizing voltage-gated Ca2+ channels
Aligning pre- and post-synaptic structures
Mediating synaptic plasticity
What proteins make up the active zone scaffold?
RIM, Munc13, RIM-BP, Liprin-alpha, ELKS.
What is the role of RIM proteins? (AZ)
They regulate vesicle docking, recruit Ca2+ channels, and influence synaptic plasticity.
What is the function of ELKS? (AZ)
It modulates the number of docked and primed vesicles and anchors Ca2+ channels.
How does Liprin-alpha contribute to active zone organization? (AZ)
It helps establish where active zones form by linking RIM and ELKS to cell adhesion molecules.
What structural feature characterizes the active zone at the Drosophila NMJ? (AZ)
The T-bar structure, formed by Bruchpilot (BRP), an ELKS homolog.
How do presynaptic and postsynaptic structures align? (AZ)
Trans-synaptic adhesion proteins mediate direct interactions.
Some evidence suggests receptor-Ca2+ channel interactions.
Diffusible signals may influence receptor placement.
What role does synaptic cleft protein distribution play in neurotransmission? (AZ)
Dense protein networks facilitate cell adhesion and receptor organization.
What are the three proposed mechanisms for synaptic alignment? (AZ)
Direct interaction between trans-synaptic cell adhesion proteins.
Direct receptor-Ca2+ channel interactions.
Diffusible signaling molecules modulating alignment.
What happens to active zones in RIM mutants? (AZ)
Ca2+ channel recruitment is impaired, reducing neurotransmitter release efficiency.
What imaging technique revealed that the T-bar structure is actually a ‘doughnut’? (AZ)
STED microscopy, which allowed visualization of BRP in Drosophila NMJs.
