week 6 lecture 1

These flashcards cover key concepts related to SNARE complexes, synaptic vesicle docking, and the role of proteins like UNC-13 and synaptotagmin in the fusion process.

What are the three main proteins involved in the SNARE complex assembly?

SNAP-25, synaptobrevin, and syntaxin.

What are primed vesicles?

Primed vesicles are fusion competent.

What is a problem with syntaxin in its default state?

It adopts a closed configuration that hides the SNARE binding domain.

What is the relationship between closed syntaxin and SNARE complex formation?

Closed syntaxin is incompatible with SNARE complex formation.

How can syntaxin be opened for SNARE complex formation?

UNC-13 binding to syntaxin promotes opening.

What mutation is mentioned that affects syntaxin?

The unc-13 mutant.

What does UNC-13 do to syntaxin?

It binds to the N-terminus of syntaxin and promotes SNARE complex assembly.

What technique preserves synapses in their physiological state?

High-pressure freezing technique.

What are the key components of synaptic vesicle docking?

Syntaxin and UNC-13 are required for SV docking.

What defect occurs in syntaxin and UNC-13 mutants?

They have synaptic vesicle docking defects.

What is depicted in high-resolution images of synapses?

The symmetrical organization of protein complexes attaching vesicles to the plasma membrane.

What regulates Munc13/UNC-13 conformations?

DAG and Ca2+.

What triggers vesicle fusion?

Calcium influx through voltage-gated calcium channels.

How quickly does fusion occur after calcium influx?

Within 200 msec.

What happens to synaptotagmin I knockout mice?

They lose synchronous release.

What role does synaptotagmin play in the fusion process?

It binds calcium and regulates fusion by interacting with SNARE complexes.

What structural change does synaptotagmin's C2B domain undergo upon Ca2+ binding?

It inserts into the plasma membrane.

What effect does C2B insertion have on the plasma membrane?

It causes the plasma membrane to dimple up inside the ring.

What is the energy barrier related to synaptotagmin's role in fusion?

C2B insertion lowers the energy barrier for fusion.

What does synaptotagmin hold together until the Ca2+ trigger?

The SNARE complex.

What are the steps leading to vesicle fusion, initiated by synaptotagmin?

Ca2+ binding, C2B insertion, and zippering of SNARE complexes.

What is the summary of exocytosis regarding Munc13?

Munc13 docks synaptic vesicles and promotes SNARE complex assembly.

What happens when Ca2+ channels open in response to action potentials?

They bind synaptotagmin, triggering vesicle fusion.

What does syntaxin's closed state prevent?

SNARE complex formation.

Which protein is responsible for the zippering of SNARE complexes?

Synaptotagmin.

What triggers the release of synaptic vesicles?

Calcium ions.

Which scientific contribution is associated with Tom Sudhof?

He won the Nobel Prize in 2013 for his work on synaptic transmission.

What happens to the Munc13 ring during exocytosis?

It docks synaptic vesicles.

What molecular mechanism facilitates the opening of closed syntaxin?

Binding of UNC-13.

What does calcium influx trigger in the context of vesicle fusion?

Fusion of the vesicle with the plasma membrane.

What structural form does syntaxin adopt when it is inactive?

Closed.

What is the effect of synaptotagmin on vesicles before calcium signal?

It clamps primed vesicles.

What do docked vesicles interact with?

The presynaptic membrane.

What is a dense core vesicle often abbreviated as?

DCV.

In which cellular location do the SNARE complexes engage for vesicle fusion?

At the presynaptic membrane.

What is the primary research focus of Betz et al. 1997?

The role of UNC-13 in SNARE complex assembly.

What do high-resolution images reveal about vesicle organization?

Symmetrical organization of protein complexes.

What are the conformations of Munc13 regulated by?

DAG and calcium ions.

In the context of synaptic exocytosis, what could a lack of calcium lead to?

Failure of vesicle fusion.

How are synaptic vesicles affected by the unc-13 mutation?

They have defects in docking.

What structure does synaptotagmin form on synaptic vesicles?

Rings.

What occurs within the presynaptic terminal when an action potential arrives?

Calcium influx triggers synaptic vesicle fusion.

What is the relationship between calcium channels and primed vesicles?

Calcium channels are in close proximity to primed vesicles.

Why is syntaxin's open form critical for SNARE complex formation?

It allows access to the SNARE binding domain.

What happens to SNAP-25 during SNARE complex assembly?

It participates in the assembly alongside syntaxin and synaptobrevin.

What study highlights the role of synaptotagmin in exocytosis?

The work leading to Tom Sudhof's Nobel Prize.

What is the result of SNARE pin clamping by synaptotagmin?

It prevents immediate fusion until calcium is present.

What role does Ca2+ play in synaptic vesicle exocytosis?

It initiates the fusion process.

What is the importance of the C2A domain in synaptotagmin?

It interacts with the SNARE complex prior to fusion.

What does the presence of DAG indicate about Munc13?

DAG regulates the conformational states of Munc13.