L15 - Neuronal Maintenance - Neurotrophins Flashcards
What structures do you find in dendrites?
mRNA, ribosomes, ER - for Ca2+ synthesis
How does receptor activation at the axon terminal stimulate responses in the cell nucleus?
Terminals of sensory neurons have receptors for NGF (during development) which, when bound, sends a signal via reterograde transport to the nucleus which determines whether the cell will undergo cell death by altering gene expression.
What is retrograde transport used for?
Membrane - bound vesicles are returned to the cell body from the distal axon.
• (i) endocytotic retrieval of synaptic vesicle membrane (vesicles of peptide NT)
• (ii) ligand-induced internalisation of receptors at clathrin-coated pits
• Mitochondria are returned to the cell body and multi-lamellated vesicles of unknown function
• Structural proteins - possibly damaged
Components of the axonal skeleton (4)
- Microfilaments (actin): 8 nm diameter - most abundant at axon terminus, interacts with spectrin (involved in cell-cell contact)
- Intermediate filaments (neurofilament): 10 nm - used as a marker to differentiate neuron from glia
- Microtubules: 24 nm diameter - made by linear polymerisation of globular proteins
- Spectrin - protein giving shape and support to cell membrane and axonal membrane by forming a lattice underneath the membrane. Globular protein that polymerises and cross-links. Binds to structural proteins such as actin and Ankyrin, and to some integral membrane proteins. It is capable of transmitting extracellular signals (sometimes from adjeacent/contacting cells) to neurofilament and microtubules
In microtubules, does transport occur on the inside or outside of the tubule
Outside
Microtubules - its function
- Axonal (and intracellular) transport
- Contribute to cell shape and strength
- Shuttle organelles inside the cell body
Microtubules - how is it synthesized?
• Synthesized by polymerisation of αβ tubulin heterodimers.
• The β end is called the + end and undergoes preferential extension and shortening and lengthening
• The α end is the – end and is the site of nucleation and anchoring
- Pattern is a b a b
How many tubulin linear filaments form a cylindrical microtubule?
13 tubulin linear filaments that interact laterally
Only retrograde, only anterograde or both occurs along microtubules?
Both
Kinesins and dyneins, which is responsible for which form of transport?
Anterograde transport - Kinesins
Retrograde transport - Dyneins
Fast Axonal Transport for membrane bound structures
- ATP-driven Transport occurs in 5 nm hops. The max speed of transport: 600 hops (3 microns) per second (=12 mm per hour)
- Vesicles carry membrane proteins (e.g. receptors, channels)
- Vesicles may contain soluble proteins, but these are to be secreted (e.g. neuropeptides) or retained within the membrane
Speed of slow axonal transport? What does it transport? What direction does it operate in?
- Speed: 1mm/day
- Structural proteins e.g. neurofilament (although mechanism is unknown)
- Cytosolic proteins required at the axon terminus e.g. enzymes for NT synthesis, actin (in polymerised chunks)
It only operates in the anterograde direction
How does kinesin and dynein transport things?
- The Mw of kinesin = 380,000.
- Each step is made by lagging head swivelling around becoming leading head (2 heads in total)
- The head region binds to the microtubules, and acts as the motor by hydrolysing ATP.
- The tail region binds to the cellular vesicles in a specific manner. Each type of membrane vesicle has its own type of kinesin motor protein.
- Kinesins move along a single protofilament of the microtubule.
- Anterograde and retrograde transport can occur on one microtubule, and the vesicles can cross without collision.
Neural circuits are not completely fixed - what are they dependent on?
- Activity dependent
* Neurotrophin dependent
What are neurotrophins?
Neurotrophins are a family of proteins (class of growth factors) that induce the differentiation, survival, development, maintenance, axonal growth and function of neurons.
