Synaptic Scaffolding Proteins

Question 1

The synaptic vesicle cycle is a x-dependent process that is driven by assembly/disassembly
of the x complexes, and assisted by molecular chaperons.

Answer 1

calcium

SNARE/SM

Question 2

what is the post synaptic density?

Answer 2

a protein-rich microdomain of the post-synaptic membrane
that contains a great variety of receptors, adhesive systems, ion channels, signalling enzymes,
and scaffold proteins.

Question 3

why is PSD95 the mosst important scaffolding protein at excitatory PSDs?

Answer 3

it modulates the

strength of neuronal transmission by acting on the clustering of glutamate receptors.

Question 4

how are gap junctions made

Answer 4

• single protein subunits connexins

- a gap junction is made of 2 hexagonal rings of connexins (called a connexon)

Question 5

when are gap junctions opened? when are they closed?

Answer 5

are fully open when [Ca2+]<10^-7 M and become narrower as [Ca2+] increases. When [Ca2+]>5x10^-5 M they
close (to protect neighboring cells from damage propagation).

Question 6

name the major 4 intracellular messengers

Answer 6

• cAMP, cGMP
• Ca2+
• IP3
• DAG

Question 7

calcium buffers are of 2 kinds

Answer 7

• cytosolic:calbindin D-28, calretinin, parvalbumin

- ER/SR buffers and chaperones: calnexin, calreticulin, calsequestrin, GRP 78, GRP 94

Question 8

name the 3 calcium pumps

Answer 8

• PMCA or SERCA: 2Ca per ATP
• NCX: 3Na in for 2 Ca out of cell
• Mitochondrial uniporter:

Question 9

for gene transcription calcium signalling usually manifests as

Answer 9

repetitive and

transient Ca2+ waves.

Question 10

use of spines on neurons?

Answer 10

individual spines can undergo
input-specific, Ca2+-dependent synaptic
modifications during the process of
learning and memory

Question 11

list the synaptic vesicle cycle

Answer 11

• Vesicles are replenished from endosomes or by recycling after exo- and endocytosis,
  and filled with neurotransmitters (NT).
• vesicles are brought closer to pre-syn membrane
• Vesicles are tethered to the presynaptic active zone in a “docking” reaction that
  depends on the synaptic vesicle proteins Rab3/27 and the active zone protein RIM.
• Vesicles are “primed” to render them competent for Ca2+-triggered fusion
• Ca2+ triggers fusion-pore opening, releasing the neurotransmitters
• Vesicles recycle:
• locally immediately after fusion-pore opening (“kiss-and-stay”, 6);
• by endocytosis via a rapid pathway that is likely clathrin-independent (“kiss-and-run”, 7);
• or by a clathrin-dependent pathway that involves an endosomal intermediate (8).

Question 12

name the proteins needed for NT release?

Answer 12

• SNARE proteins: synaptobrevin, syntaxin-1, SNAP-25.
• SM proteins: Sec/Munc18 protein. It remains associated with syntaxin-1
  throughout the cycle.
  *Synaptotagmins: Ca2+ sensors for exocytosis.
  *Chaperones: catalyse SNARE complexes’ association and dissociation.
  *Complexin binds to the partially assembled SNARE complex during
  priming and acts as an adaptor for synaptotagmins .

Question 13

explain the SNARE/SM protein cycle?

Answer 13

Priming I: tethered vesicles are primed for fusion by opening up the
closed conformation of syntaxin-1 and partially assembling the SNARE
complex.
Priming II: complexin binds to the SNARE complex to “super-prime” it and
trigger vesicle fusion.
Synaptotagmin binds Ca2+ and changes its folding. In the new
conformation, it displaces complexin and triggers fusion-pore opening.
After fusion-pore opening the pore expands and SNAPs are recruited to
displace SNARE complex, and the pore expands.

Question 14

How do Ca2+ channels properly localize close to tethered vesicles?

Answer 14

pics

Question 15

what are the 3 adhesive systems?

Answer 15

neurexins, neuroligins
caderins
immunogloblin superfamily cell adhesion proteins

Question 16

neurexins are

Answer 16

adhesive proteins of the pre-synaptic membrane.
Neurexin ligands (on the post-synaptic membrane) are: neuroligins, dystroglycan and neuroxophilins.

Question 17

cadherins are

Answer 17

type-1 transmembrane proteins
- role in cell adhesion
- dependent on calcium ions
- intracellular cytoplasmic tail
associates with catenin and other proteins called the cadherin adhesome

Question 18

what is DSCAM

Answer 18

is a Down syndrome cell adhesion molecule. When this gene is over-expressed in the developing fetal
central nervous system, it leads to Down syndrome.

Question 19

where are excitatory synapses found

Answer 19

on tiny protrusions called dendritic spines.

Question 20

where are inhibitory synapses forund?

Answer 20

on the shaft of

dendrites, or on cell bodies and axon initial segments.

Question 21

what scaffolding protins are needed at the PSD

Answer 21

PSD95
A-kinase anchoring protein (AKAP)
Homer
SAP97
SAP90/PSD95 –associated protein (SAPAP)
SH3 and multiple ankyrin repeat domain (Shank ) family

Question 22

explain PSD95

Answer 22

It belongs to the membrane-associated guanylate cyclase proteins.
It contains PDZ domains and an inactive guanylate kinase-like domain.
SH3-GK domain promotes the clustering of AMPAR , which influences signal strenght