Cytoskeleton

Question 1

What is the cytoskeleton

Answer 1

—> determines shape of the cell

—> responsible for asymmetric distribution of organelles within the cytoplasm

—> three types of protein structures: microtubules, neurofilaments, microfilaments

Question 2

Microtubules

Answer 2

• form long scaffolds that go from one end of neuron to the other
• play key role in developing and maintaining cell shape
• constructed of protofilaments that consist of tubulin subunits
• Tubulin subunits bind to each other along protofilaments
• have polar structure (negative end oriented towards centre of cell, positive end towards the periphery)
• grow by addition of GTP bound tubulin dimers at positive end

Question 3

Neurofilaments

Answer 3

• bones of the cytoskeleton
• most abundant fibrillar component in axons
• more stable than microtubules
• fibers that are twisted around each other to produce coils

Question 4

Microfilaments

Answer 4

• smallest fibers
• arranged in a helix
• short
• concentrated at cell’s periphery
• form dense network
• play key role in dynamic function of the cell’s periphery e.g. motility of growth cones, during development, generation of specialized microdomains at the cell surface, formation of pre- and postsynaptic morphological specializations

Question 5

What’s cool about microtubules and microfilaments?

Answer 5

—> dynamic state of microtubules and microfilaments allows mature neurons to retract old axons and dendrites and extend new ones
—> thought to be major factor in changes in synaptic plasticity

Question 6

Microtubules are involved in cargo transport

Answer 6

• microtubules act as tracks for transport- due to polarity, each motor only drives its cargo in only one direction
• kinesin transports cargo from cell body to axon terminal
• dynein transports cargos from axon terminal back to cell body
• myosin proteins transport cargo to their final destination
• in axons, microtubules have a regular orientation (positive pointing out, negative facing in)

—> allows some organelles to move toward and other away from nerve endings

—> maintains distinct distributions of axonal organelles

• in dendrites, microtubules with opposite polarities are mixed together

Question 7

Transport mechanism

Answer 7

• most organelles are made in the cell body and need to be transported to the axons –> essential for growth and survival
• organelles include synaptic vesicles, proteins, mitochondria

Fast vs. Slow Transport

• –> axonal transportation can be fast or slow, retrograde or anterrograde

Fast transport: vesicular cargo in both directions

slow transport: cytoskeletal proteins

• mechanism poorly understood until recently due to advancements in imaging techniques
• actually rapid BUT frequent pauses - stop/go model
• only towards terminals

Question 8

Protein synthesis

Answer 8

• some mRNA is encoded locally to make proteins for dendrites –> proteins needed for making microtubules, microfilaments, receptors etc.

Local protein synthesis solves several problems

• protein transport over long distances not needed
• protein can be synthesized where it is most needed
• local regulation of where protein is made
• rapid protein synthesis in response to synaptic signalling
• newly formed proteins can help modify synaptic signals –> may result in regional remodeling of dendrites and synapses according to synaptic activity