,Lecture 1 Neuronal organelles
Neuron fact sheet: AIS = axon hillock, makes sure that neurons are polarized and
remain that way
• Highly polarized and compartmentalised
• Transmit, receive and process signals at distant locations (synapses)
Active zone = zone where membrane fusion of the vesicles
from synapse to post synapse takes place (on the synapse)
Neuron challenges:
• with whom to make contact
• How to get to the right place in the brain
• Neurons need to move from the VZ to the membrane
• How to generate and maintain polarized • Neurons axon makes contact with multiple postsynapses
• How to supply distant synapses with proteins & lipids (probability depends on proteins that fit together)
• How to maintain energy levels in different synapses
• How to respons to changes in local environment and events
Synapses: Information processing and transmission nodes
• requires energy, proteins and lipids
The major organelles required for neuron and synapse function:
• Mitotic cells: Nucleus —> ER (rough - smooth) —> ERGIC —> Golgi (cis - trans) —> TGN —> secretory granule
Organelle Organisation in neurons:
• Morphology - ER - ERGIC - GA - RE
,ER:
• continuous network in soma, dendrites and axon
• present in pre- and postsynaptic terminals
• allows local protein translation
• major calcium store
• Major lipid source
Membrane contact sites: ER forms continuous dynamic network (ER shaping
protein allow for mobility)
• Lipids transfer
• Calcium exchange
ER supplies calcium to mitochondrion
• Interactions are dynamic
ER supplies membrane with lipids and to receive calcium
ER is super dynamic and makes contact with all organelles
ER-PM contact sites in calcium homeostasis and axon growth
Calcium elevated, then it binds to ORAI which makes a channel to refill the ER with calcium
, ERGIC
• Receives COPII coated vesicles from ER
• Receives COPI coated vesicles from Golgi
• Role in folding and quality control nascent proteins
• Role in glycolysation of proteins
ER is everywhere, but the Golgi is not
Golgi (GA):
• We cannot make fully glycosylated
• Mainly present in somas (GOs in some dendrites) proteins in the axon
• neuron transport locally makes membrane
• Main organelle for post translation modifications proteins via vesicles and transmembrane
proteins
• Main organelle for sorting cargo
• Three subzones: Cis, Medial and trans
Golgi dependent and Golgi independent secretory routes in dendrites:
Evidence for local translation of mRNA
visualizes the transport of a fluorescent protein from ER to Golgi to
RUSH system: to synchronise secretory protein trafficking Plasma membrane
• Streptavidin Biotin interaction
• Retention using selective hooks
Hook = protein localized to ER or Golgi tagged with streptavidin
Reporter = protein of interest tagged with streptavidin binding protein (SBP)
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