Synapse Formation Flashcards
What are muscles innervated by?
Motor neurons
What are the 3 cells involved in neuromuscular junction synapses?
- Axon terminals
- Muscle fibres
- Schwann cells
Where do synapses happen in the muscle?
- Synapses made at shallow depression in muscle
- Sarcolemma invaginated at syapse to form deep, regular post functional folds
What is a post junctional fold?
Present at the troughs and crests:
- at crest: loads of ACh receptors
- at troughs: lots of voltage gated Na+ channels
Outline the basic process of the neuromuscular synapse.
- single transmitter ACh released froma axon
- single NT type - nicotinic AChR expressed on post synaptic membrane
- motor neuron forms a bouton above synapse, surrounded by schawnn cell, bouton contains large number of synaptic vesicles and synaptic vesicle dockery and fusion proteins
Where is ACh receptor expressed?
On surface of muscle cell
How are AChR pre-patterened to the centre of muscle fibres before motor axons arrive?
AChR clusters are stabilised at synaptic sites whilst extra AChR is lost. Muscle secretes neurotrophic factors to promote for survival of innervating motor axons
How are short opening periods of the AChR achieved after motor axon innervation?
- AChR made of 4 subunits: α, γ, β, δ - characterised when receptor bind to receptor and ion pore
- After motor neuron axon is innervated, muscle fibre gets change in composition of AChR, get v short opening periods allow high level of current to flow through
How is expression of post-synaptic AChRs induced? (8 marks)
- Innervating motor axons secrete proteoglycan Agrin - this binds to Lrp4
- Agrin/Lrp4 form complex with dimers of TRK Musk - each Musk molecule is phosphorylated at tyrosine residue Y553
- Y553 phosphorylation recruits Dok7 adapter protein leading to its dimerization and phosphorylation
- Dok7 dimeriation and phos, increases Musk activity and recruits Crk/ Crk-L
- JNK and Rho/ Rac GTPase activation results in Rapsyn binding to AChR cluters and their stabilization
What do motor axons do at a potential synapse?
What does this suggest about Agrin and Musk signalling?
(4 marks)
- Don’t stop growing and develop synaptic boutons at presumptive synapse
- They express AChR
- Suggests agrina nd musk signalling generates a muscle derived trophic molecule required for synaptic bouton formation and maturation
What have transgenic mice revelead the importance of Musk, Lrp4 and Dok7?
That they are all essential for expression of central motor neuron AChR clusters before innervation
Where is the only place that synapses can be made in the CNS?
Dendritic shaft - as they can be both inhibtory as well as excitatory
Name a few of the pre-synaptic proteins in the pre-synaptic zone. (4 marks)
Synaptic vesicle
Fusion proteins
Synaptic vesicle docking proteins
Scaffolding proteins
Why are post synaptic membranes electron dense?
High level of neurotransmitter receptors expressed and scaffolding proteins
What do scaffolding proteins do in the pre-synaptic zone?
Form structure for docking fusiom proein to bind to e.g. Piccolo (scaffolding protein)