The Cytoskeleton Flashcards
Component of Cytoskeleton?
Microtubules, microfilament, intermediate filament, and accessory and regulatory proteins
Microtubules composition and shape.
Protein
Shape
Associated with
Polymer of tubulin dimers : alpha tubule and beta tubulin.
Composed of 13 (+/-) Protofilaments (stacks of tubulin dimers)
Tubulin is a GTPase: it hydrolyzes GTP to GDP releasing energy.
Hollow cylinder with a dimeter of 24nm making it largest of all filaments.
It ‘s associated with accessory proteins called microtubules- associated proteins (MAPs) that stabilize and space the polymers and regulate interaction between the cytoskeletal elements.
Properties of microtubules
dynamic
and acts as a?
Highly dynamic. Undergoes bouts of assembly and reassembly.
Acts as a substrates for microtubule based motor protein (dynein and kinesin) to transport cargo.
polymerization structure of microtubules
talk about the different ends
Polarized polymer with a plus and minus end.
Plus end is the dynamic end that lengthens and shortens.
Functions of MT
Make up the mitotic spindle- cell division.
High way of the cells - transport.
Provide railways for organelles transport in most interphase cells.
Key determinant of cell shape
Very important for neurons for cell shape and axonal transport
Provide backbone for cilia and flagella.
Microtubule polarity and dynamic
where are the ends of MT embeded ?
Positive end is the dynamic one- faster rate of tubulin addition and removal.
Negative end- slower rate of tubulin addition and removal.
The negative end is embedded within the centrosome while the positive end is towards the periphery of the cell.
MT dynamic instability
Refers to the behavior of the positive end of the MT where it polymerize and depolymerize over and over.
Rapid depolymerization is referred to as catastrophe.
Rescue refers to the polymerization phase of MT following a catastrophe.
Every time a MT is growing it is a rescue phase.
Polymerization occurs at the positive end o the MT. Tubulin is a GTPase, it has to be loaded with GTP before it gets polymerized.
As a function of time, most of the MT will have a GDP bound tubulin, while the plus end where the newly incorporated tubulin will have a GTP bound to them, referred to as the GTP cap of the plus end.
Now when a catastrophe happens we stop having the GTP loaded tubulin added to the plus end. Now we only have the GDP bound tubulin that was already in the microtubule. The GDP bound tubulin has a higher probability of falling off the plus end, so we get the catastrophe period where the MT is now shrinking.
Microtubules associated MOTOR proteins
and structure.
chains
Dynein and Kinesin.
Dynein moves towards the negative end (center of the ell)
Kinesin moves toward the positive end of the cell..
Both use ATP as energy source that allows them to walk along the MT
They are made up of heavy chains that make up the head domain which interacts with the MT.
They also have light chains or light and intermediate chains. The functions of these light chains is the regulate the function of the motor proteins whether it’s on or off, or how fast it actually goes, AND control what the motor protein is bound to.
There are many types of light and intermediate chains that bind the heavy chains of the motor proteins which gives the Motor proteins specificity
Dynein: made up of head domain and base. the base is made up of light and intermediate chains.
Kinesin: made up of head domain, coiled coil , and a tail that is made up of light chain.
Microtublules associated proteins (structural non-motor proteins)
Functions
Like Tau.
Organize MT
Regulate MT stability (how long a MT would stick around in the cell)
Regulate MT dynamics
Microtubule Organization and Nucleation Center
what other organelles nucleate MT ?
THE CENTROSOME.
Nucleation occurs at the centrosome.
This is where the negative end of the MT is born.
The negative end emanate through nucleation ( the genesis of a polymer) from the centrosome.
The positive end emanate through polymerization (elongation) and fills the cytoplasm.
recent research indicates that the Golgi fragments may also nucleate MT
Cilia and Sperm Flagella
what nucleates them
Microtubules based structures for movement.
Cilia is found in the lung epithelium, trachea, fallopian tube.
function as a mucociliary escalator for, e.g to move phlegm.
They are apical projections found at the surface of the cell. This is one of the cases where the nucleation doesn’t happen at the centrosome.
They are nucleated from the basal body!!
The basal body also uses gamma tubulin to nucleate MT that gives rise to the cilia.
so the structure of the MT within a cilia is that they have a basal body just underneath the plasma membrane.
The - end is embedded within the basal body and the + end projects to the tip of the cilia.
Centrosome structure
what protein is found there
what is the process
Two microtubules in the center aligned perpendicular to each other. This is the core of the centrosome.
There’s also abundance of other proteins attached to it.
one of the most important proteins found in the centrosome is Gamma tubulin. it is required ONLY for nucleation.
It is a type of tubing that forms a little ring that alpha and beta dimers start to be added to that first ring that is made up of gamma tubulin.
YOU DO NOT FIND ANY GAMMA TUBULIN ALONG THE MT they are all alpha beta dimers.
Mucociliary escalator
Motile cilia that keeps you alive.
It moves mucus up and out into our oral cavity from our lungs.
it prevent us from suffocating on our own mucus.
This happens bc the cilia beats and move mucus. Hence the name
if it malfunctions= primary ciliary diskinesia
Made up of microtubules.
The axoneme
general term for cilia and flagella like structures.
Arranged in 9+2 (2 pair in the center and 9 pair around).
in between 9+2 there is a dynein connections. Dynein is not moving cargo, but instead moving the MT relative to each other.
Dynein is what allows the microtubules to bend by sliding MT relative to each other
Disease associated with malfunction of microtubules based cellular structures
Immotile cilia syndrome (aka primary ciliary dyskinesia) - body wide defect in axonemal structure that result in obstructive lung disease and sterile males- Bc mucociliary escalator doesn’t move and sperm doesn’t move
Karatgener’s syndrome - syndrome is characterized by the combination of primary ciliary dyskinesia and situs inversus. Situs inverses is the reversal of normal body asymmetry where the organs are flipped.
Cancer- cell division depends on MT. Taxol is a cancer drug that disrupts the MT dynamics to block cell division. It binds MT and stabilize them so they cannot be depolymerized which is just as bad bc MT are constantly going dynamic instability and if that is prevented that it will cause problems in cellular based physiology
Diseases associated with mutations/alteration in microtubule proteins.
Lissencephaly- smooth brain due to a mutation in microtubule proteins LIS 1 and doublecortin.
Charcot-Marie-Tooth disease type 2A- Mutation in specific kinesin (neurologic)
Neurodegenrative disorders- mutations in tau, kinesin, spastin.
Neurotropic Viruses
Viruses that when they infect the body they go to the neurons by hitching a ride on the MT
Ex: herpes virus.
virus gets in through a cut in the body. find nerve endings of the cell and bind it. Virus takes a ride on dynein on the MT to the cell body. The they replicate and take a ride on Kinesin to the nerve ending to release viral particles and cause disorders.
