Summary, Cell biology of neuron and glia
Lecture 1, Neuronal organelles and their function
Neuron fact sheet
• 86 billion neurons with a total of 1 x 1015 synapses (the synapse can carry out tasks and
decisions without the need of the soma as this is too far from it)
• Post mitotic→ once they are at their place, they need to remain there the rest of your life.
However, earlier was thought all neurogenesis was in embryogenesis but this is not the case,
in the hippocampus, in later stages of life there is still neurogenesis.
• Highly polarized→ They have long axons and shorter dendrites and many synapses
• Highly compartmentalised
• Transmit, receive & process signals at distant locations (synapses)
Neurons face many challenges
• How to get to the right place in the brain
• With whom to make contact
• How to generate and maintain polarization
• How to supply distant synapses with proteins & lipids
• How to maintain energy levels in distant synapses
• How to respond to changes in local environment and activity
Synaptic vesicles come from an axon and should not go into dendrites but into the axon.
These vesicles fuse at the presynaptic terminal at the position of the active zone.
,Synapse function requires energy, proteins and lipids
In the active zone, the synaptic vesicles fuse, it is called an active zone because calcium
channels are located there. There are proteins that approximate these vesicles in close
proximity (priming and docking→ specific for pre-synapses).
With super-resolution imaging, we can see that there are microdomains from calcium
channels to proteins on the pre-synaptic receptors making an alignment between the pre-
synaptic side and the post-synaptic receptors, so the time of signal transmission is minimized
and timed.
In the axon initial segment are action potentials generated but it also acts as a barrier for
proteins that have to go into the dendrite and not go in the axon. It thus makes sure neurons
are polarized and stay polarized. If you would delete it proteins that should be in the post-
synapse will be in the pre-synapse.
The postsynaptic density is darker coloured as all the receptors are located there.
On the electron microscopy image, you can see the two most studied synapses.
• The neuromuscular junction has a lot of organelles and mitochondria. This synapse
has two active zones. In your brain synapses, you have often only one active zone
while in the muscular junction, there are two which is important because of their
high-release probability, more vesicles can fuse and be released for a longer time.
• The synapses in the hippocampus, with only one active zone.
Random:
Zip-code: These sequences of nucleotides, or what scientists refer to as RNA “ZIP codes,”
are recognized by proteins that act like mail carriers and deliver the RNAs to where they are
supposed to go.
,The SER is generally used for the creation/ storage of lipids and steroids, while the RER plays
a significant role in the synthesis of various proteins. The RER is termed "rough" due to
ribosomal attachments to the surface compared to the SER, which does not have ribosomes.
In the Golgi, there is a lot of posttranslational modifications like glycosylation and sorting for
transport.
What are the major organelles required for neuron and synapse function?
The mRNA leaves the nuclear envelope and is then translated and migrates into the ER.
Transmembrane proteins are formed in the ER and leave in vesicles via the ER exit sites. They
then pass the ER Golgi intermediate complex (ERGIC) and then go into the Golgi. In the Golgi,
the proteins mature a bit more but they are still immature and are glycosylated with
posttranslational modification. Then they will enter the TGN where they are sorted
(constitutive release; …). On their way to the plasma membrane, they will mature: and will
contain the proteins needed to fuse with the membrane (SNARE). This was believed until 10
years ago.
, Organelle organisation in neurons
Organization of Cellular Secretory Organelle: ER
- continuous network in soma, dendrites & axon
- Present in pre- & postsynaptic terminals
- Allows local protein translation → They think that one synapse will become very active,
however, they do have a low lifetime (they do not go to the Golgi)
- Major calcium store
- Major lipid source (one big lipid bilayer)
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