exam 1 Lecture 3 + beginning of lecture 4 Flashcards

1
Q

What is responsible for the movement of AMPARs, how does the movement start and how is this movement carried out?

A

PICK1. It removes the calcium impermeable receptors in response to calcium influx through NMDARs. PICK1 stays bound to the CIP receptors until more calcium influx makes it sequester the receptors to the membrane for insertion. PICK1 dissociates from CIP to allow them to get inserted.

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2
Q

Why are unedited GluA2 containing receptors important?

A

They are in children, and they are calcium permeable. This means the early synapses are really strong because their open times and conductances are high. Each input has a greater impact at the early embryonic and postnatal stage.

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3
Q

What determined that AMPARs are not required for LTP?

A

The researchers replaced AMPARs with Kainite receptors and the animals lived. They were able to initiate the LTP there too.

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4
Q

What did researchers discover is required for LTP?

A

A pool of extrasynaptic receptors that you can track at the post synaptic specialization.

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5
Q

What is the slot hypothesis and why is it false?

A

The slot hypothesis states that LTP makes more binding sites for all types of glutamate receptors, so even kinate receptors could replace AMPARs for LTP. This is false for two reasons:

  1. phosphorylating TARPs does not increase their association with AMPARs.
  2. Kainate phosphorylation increases their mobility and not their stability at the post synaptic specialization.
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6
Q

What are anchoring proteins and what was thought to be their function. Why was this wrong?

A

They are present at the subsynaptic specialization that function to anchor glutamate receptors at the post synaptic specialization. This is false because the proteins interact with actin, so the TARPs and AMPARs don’t directly interact with them.
- pathway in notes.

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7
Q

What are scaffolding proteins?

A

They anchor glutamate receptors at the post synaptic density. They crosslink glutamate receptors to actin.

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8
Q

How were scaffolding proteins discovered?

A
  1. homogenize tissue
  2. centrifuge and remove large parts
  3. centrifuge again
  4. remove the supernatant and keep the synaptosomes.
  5. Visualization showed that there is a tight connection between the post synaptic and presynaptic specializations so the synapses are not disturbed through the centrifugation process.
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9
Q

What keeps the pre- and post-synaptic specializations in registration? Why is this type of registration advantageous?

A

Cadherins tether the specializations close to each other. The registration is advantageous because the release sites are really close together.

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10
Q

What is the function of PKC

A

It blocks kinases that inhibit LTP, and is involved in LTP3. It is normally inhibited by a pseudosubstrate site.

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11
Q

How do you know if ZIP blocks other forms of PKC?

A

Do an in vitro test with various forms of PKC. ZIP doesn’t block them or interfere with LTP1 formation.

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12
Q

What is PKM-zeta and what is its mechanism?

A
  • It inhibits the endocytosis of AMPARs.
  • increase in calcium removes PIN1 from PKM-Zeta mRNA. PKM-Zeta folds into its proper protein shape. PKM-Zeta phosphoinhibits PIN1.
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13
Q

What is the synaptic tagging hypothesis?

A

The synaptic tagging hypothesis states that the spines that receive the tetanus have a tag that allows them to capture the plasticity related proteins.

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14
Q

What receptors do stargazin and PSD-95 bind?

A

Stargazin binds AMPAR. PSD-95 binds NMDAR.

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15
Q

Why is anchoring important?

A

Proteins in the post synaptic space anchor the receptors or else the receptors will diffuse out everywhere.

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16
Q

What two molecules are implicated in anchoring and how does this work?

A

Actin and CamK2. Actin is there to support the spine during LTP because as it grows, it needs more actin to stabilize it. Normally, actin and CamK2 are bound together. When calcium enters during LTP, Calcium binds to CamK2. This dissociates CamK2 from actin. This allows actin to grow. More calcium makes CamK2 bind to actin again.

17
Q

What is the structural role of CamK2?

A

It cross links parallel actin filaments along the spine.

18
Q

What is the purpose of LTD and how to initiate it?

A

It starts from a low frequency stimulus or action potential. It weakens post synaptic synapses that are not needed anymore and reverses the effects of LTP.

19
Q

Mechanism of LTD?

A
  1. Calcineurin activated by CaM. Calcineurin binds PP1, which dephosphorylates CamK2 and prevents CamK2 from phosphorylating GluA1.
  2. CaM also activates Adenylyl Cyclase. Eventually PKA is activated. Then you phosphorylate proteins that prevent gene transcription. Therefore, AMPARs don’t get stabilized.