Lecture 18- Postsynaptic density

Question 1

Where do synapses occur?

Answer 1

• synapses occur on dendritic spines, (the knobs) that is where the synaptic connection is
• generally the postsynaptic density is there

Question 2

PIC1How does postsynaptic density look like?

Answer 2

• the postsynaptic density is black as it has dense protein in there, more then presynaptic terminal even
• extremely protein dense

Question 3

What sort of proteins are there in the postsynaptic density?

Answer 3

• lot of the proteins are clusteirng proteins, that hold the receptors together, synapses in the CNS, excitatory glutamargic one, two main forms of glutamate receptor NMDA and glutamate receptor, most synapses have all three forms of glutamate receptor NMDA, AMPA, and mGLuR, they respond to glutamate in complex ways
• AMPA are not on the snyaptic temrinus but nearby -several clustering proteins whose job it is to hold the receptors together
• main one is the PSD-95
• at the NMJ the equivalent of PSD-95 is agrin which is made by muscle cell
• psd95 holds signalling proteins as well CaMKII (calcium modulin kinase type II)
• also many others, important RTK (nerve growth type receptor also held here by psd95) names of receptor, psd95 and agrin and CaMKII! know these

Question 4

What are the adhesive factors holding synapses together? (initial linkage)

Answer 4

• cadherins and protocadherins
• sequence of adhesion molecules that hold the two ends together, first to form are cadherins and protocadherinsthese are repsonsible for the initial linkage,

Question 5

What are the inductive factors holding synapses together?

Answer 5

• synCAM
• EphrinB/EphBR

-Neurexin

-Neurolignin

• Neuregulin
• cytoskeletal specialization of the active zone
• inductive factors -postsynaptic density proteins
• then molecule called synCAM (synaptic cellular adhesion molecule) also adds adhesive force between the two ends)

Question 6

What is the importance of neurexin and neuroligin in holding the pre and postsynaptic membrane together?

Answer 6

• two of the main important proteins in the synaptic
• one is supplied by the presynaptic membrane (neurexin) and the other by the postsynaptic membrane (neuroligin)
• they lock synapse into place and bind to each other, act as receptors for one another, form a tight complex
• there are a lot of these but do not obstruct the passage of neurotransmitter
• neuroligin also has an intracellular structure

Question 7

What is the connection of postsynaptic density and autism?

Answer 7

• turns out in certain genetic forms of autism, there are many forms however (genetic), the defect is in the postsynaptic density, Shanck, neuroligin
• autism covers a wide spectrum of childhood disorders
• gephyrin, psd95 , neroligin -in some cases have mutations that cause autism
• we don’t understand the cause of most autisms, but the genetic ones we know that tehy involve proteins in postsynaptic density