Articles Flashcards
Paper 1: Science 2000 Synaptic Assembly of the Brain in the Absence of Neurotransmitter Secretion
- What does this paper describe (what is researched here)?
- What is the main result of this paper?
- What does this result implicate?
- What the effect is of deletion of Munc18-1 protein in a mouse brain.
- Deletion of Munc18-1 results in lack of synaptic transmission.
- The brain forms normally, showing that synaptic transmission is not required for proper brain formation.
Paper 1: Science 2000 Synaptic Assembly of the Brain in the Absence of Neurotransmitter Secretion
- What kind of protein is Munc18-1?
An essential protein for neurotransmitter release.
Paper 1: Science 2000 Synaptic Assembly of the Brain in the Absence of Neurotransmitter Secretion
- What is seen in Munc18-1 deficient mice?
- Munc18-1 deficient mice lack synaptic transmission, but neurons do differentiate normally, exhibit spontaneous action potentials and perform normal pathfinding. So lack of neurotransmitter release does not impair correct assembly of the brain.
- But, neuronal networks can not persist. After assembly of neuronal networks, neurons undergo apoptosis, leading to neurodegeneration.
Paper 1: Science 2000 Synaptic Assembly of the Brain in the Absence of Neurotransmitter Secretion
- Is neurotransmitter secretion necessary for synaptic connectivity?
- Is neurotransmitter secretion necessary for proper brain formation?
- No
- No
Paper 2: Nature 2002 Regulation of AMPA receptor lateral movements
- What does this paper describe (what is researched here)?
- What are the main results of this paper?
- It describes (for the first time) that AMPA receptors are mobile and alternate between rapid diffusive and stationary behaviour.
- It is seen that during neuronal maturation AMPAR is stationary and that intracellular calcium rise riggers immobilization and local accumulation on the neuronal surface to regulate AMPAR numbers at synapses.
Paper 2: Nature 2002 Regulation of AMPA receptor lateral movements
- What did the authors do in this experiment?
They attached 500 nm latex beads to the GluR2 AMPAR subunit using an antibody against the extracellular domain of GluR2 to study AMPAR dynamics.
Paper 2: Nature 2002 Regulation of AMPA receptor lateral movements
- What is seen in regard to AMPAR?
- It alternates within seconds between rapid diffusive and stationary behaviour.
Paper 2: Nature 2002 Regulation of AMPA receptor lateral movements
- What happens during maturation?
During maturation, stationary periodes increase in frequency and length, often in spatial correlation with synaptic sites.
Paper 2: Nature 2002 Regulation of AMPA receptor lateral movements
- What happens when there’s calcium influx?
It triggers rapid receptor immobilization and local accumulation on the neuronal surface.
Paper 3: 2006 Cell Molecular Anatomy of a trafficking organelle
- What is the main focus of this paper?
The characterization of the composition of synaptic vesicles.
Paper 3: 2006 Cell Molecular Anatomy of a trafficking organelle
- How were synaptic vesicles purified from the brain?
- How were the purified synaptic vesicles analysed?
- Purification was done by a modified version of a fractionation protocol (high speed centrifuge sorting molecules based on their density)
- Based on non-quantitative (MS and SDS-page) and quantitative experiments (immunoblotting/western or dot blotting and calculating average physical parameters)
Paper 3: 2006 Cell Molecular Anatomy of a trafficking organelle
- Why is this paper important for understanding synaptic vesicle fusion?
This paper is important since it’s one of the first papers that describes how the average synaptic vesicle looks like, what proteins reside on the vesicle and specifically how many of the each type of proteins reside on the vesicle. With this knowledge, we can understand synaptic vesicle trafficking much better.
Paper 3: 2006 Cell Molecular Anatomy of a trafficking organelle
- What is meant with the fact that synaptic vesicles are no longer icebergs in a sea of lipids but also not only lipids stuffed with proteins (like a cobblestone path)?
It is a mixture of both.
- The iceberg in a sea of lipids, would mean that in a sea of lipids you can sometimes find a big pile of proteins pushed together. This doesn’t make sense, since the paper explains that the membrane is composed of much more proteins than previously thought.
- The lipids stuffed with proteins, would mean that there are so many proteins that the membrane really is stuffed with proteins where you can sometimes find lipids. But, this would mean that the membrane is no longer flexible. So this is also not the case, because vesicle membranes need to be flexibel.
So that’s why it’s a mixture of both. There are many proteins, but at some places in the membrane you need the sea of lipids to have some flexibility.
Paper 4: 2003 NatNeuro Activity level controls postsynaptic composition and signaling via the ubiquitin-proteasome system.
- What does this paper show?
Long-lasting global changes in the molecular composition of the post-synaptic density (PSD) dictated by synaptic activity.
Paper 4: 2003 NatNeuro Activity level controls postsynaptic composition and signaling via the ubiquitin-proteasome system.
- What was associated with activity-dependent remodeling?
Altered protein turnover (corresponding with increases or decreases in ubiquitin conjugations of synaptic proteins and requiring proteosome-mediated degradation).
