HTHSCI 1DT3 Lecture 3: 1.1 Cells.9
23 Jun 2018
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Vesicles bud off from Golgi, and travel to all
directions. But will only fuse with membranes
of the target compartment (axonal or
somatodendritic regions), and will not
function/fuse in other parts where it may be
wrongly delivered to.
Selective retention –
Vesicles may fuse with all areas (axons and
somatodendritic compartments). However,
only vesicles that are in the correct area will be
kept/used. Wrongly delivered material will be
endocytosed away from the cells.
How do mature neurons maintain distinct axonal and
somato-dendritic membrane compartments? –
Using PHYSICAL BARRIERS
Cell adhesion molecules (LI) which are anchored by
their cytoskeleton form a fence that prevents anything
(including lipids) from passing through.
Paper – Accumulation of anchored proteins form membrane diffusion barriers during neuronal
polarization (2003) – Nakada et al.
Confirmed that a diffusion barrier exists (at the initial segment?) – indicates how the barrier functions.
Approach:
Labelled and tracked movement of individual lipid or protein molecules in initial segment (IS),
dendrite, axon, cell body, glass.
For the labeled lipid, they used an unsaturated phospholipid (DOPE –
dioleoylphosphatidylethanolamine) that is highly mobile in the membrane.
Labelled DOPE with a flurophore (Cy3-DOPE) or a 40nm gold particle (G-DOPE) and
measured the extent of diffusion and diffusion coefficients, when inserted in either IS or
dendrite, or on glass coverslip.
How is lipid diffusion blocked at the IS (initial segment)
Cytoskeleton –
The major components (actin and ankyrinG) become highly concentrated in the IS
during development
A diffusion barrier (picket) is formed in the IS membrane through accumulation and
immobilization of transmembrane proteins on the sub-membranous cytoskeleton in the
initial segment.
(Cross reference with following lectures:)
Development: Anita Hall’s lectures
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Development: Anita Hall’s lectures
Growth/renewal: Lectures on Regeneration; Stem Cells
Morphology & Intracellular architecture: Introductory sections of most neuro text
books; Alberts.
Neuronal Polarity & Trafficking. (2003). Horton & Ehlers. Neuron 40, 277-295.
Astrocytes and Radial Glia
Glia can be subdivided into:
Macroglia – (Schwann cells, oligodendrocytes, astrocytes/radial glia, olfactory
ensheathing cells)
Microglia
Development of Astrocytes
CNS glia arise from the ventricular zone of the neural tube (similar to CNS neurons). C.f.
Schwann cells that arise from the neural crest (as do PNS neurons)
Astrocytes and neurons arise from common progenitor cells in the neuroepithelium (perhaps
even radial glia?)
Astrocyte Cell Biology
Astrocytes can be:
FiBROUS (TYPE II)
These contain much fibrous material (GFAP) and are prevalent in myelinated nerve
bundles in the white matter. These astrocytes are star shaped.
PROTOPLASMIC (TYPE I)
These have less GFAP and are abundant in the grey matter around cell bodies, synapses
and dendrites.
GFAP – an intermediate filament protein that is expressed in astrocytes and radial glia. It is a useful
marker for these cells.
In the brain and spinal cord, astrocytes have:
Many thin processes around:
Capillaries (top left on diagram)
Synapses
Surfaces of neurons
Cytoskeleton
Intermediate filament (GFAP)
Microtubules
Actin
Type II Astrocytes are
more fibrous.
Glycogen granules (large energy
stores)
Rough ER, Golgi Apparatus
Large Nucleus
Watery Cytoplasm
Functions of astrocytes and radial glia
Astrocytes interact intimately with neurons
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Astrocytes form large syncytial interconnected networks coupled by gap junctions
This has been shown by injecting dyes into a single astrocyte and seeing the dye spread through
the network.
Gap junctions allow exchange of ions and small molecules <1kDa.
Functions of Astrocytes:
At blood brain barrier, they act as a gateway between general circulation and the neurons of
the CNS (neurovascular unit)
The blood-brain barrier is formed by very tight associations of brain capillary
endothelial cells.
It is essential for controlling entry of molecules and ions from the general circulation
into the central nervous system.
Astrocytic endfeed wrap endothelial cells, providing a gateway for nutrients into the
CNS and removal of metabolites from the CNS.
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Document Summary
Vesicles bud off from golgi, and travel to all directions. But will only fuse with membranes of the target compartment (axonal or somatodendritic regions), and will not function/fuse in other parts where it may be wrongly delivered to. Vesicles may fuse with all areas (axons and somatodendritic compartments). However, only vesicles that are in the correct area will be kept/used. Wrongly delivered material will be endocytosed away from the cells. o. Cell adhesion molecules (li) which are anchored by their cytoskeleton form a fence that prevents anything (including lipids) from passing through. Paper accumulation of anchored proteins form membrane diffusion barriers during neuronal polarization (2003) nakada et al. Confirmed that a diffusion barrier exists (at the initial segment?) Labelled and tracked movement of individual lipid or protein molecules in initial segment (is), dendrite, axon, cell body, glass. For the labeled lipid, they used an unsaturated phospholipid (dope dioleoylphosphatidylethanolamine) that is highly mobile in the membrane.
