Cytoskeleton Flashcards
How does cytoskeleton make cells move?
A cell receives a signal on the other side of where the large filamentous polymer.
The large filamentous polymer, they are non covalent, quickly degrades to smaller protein subunits and then reassemble on the side of the signal.
The reassembling of primarily actin filaments creates a leading edge which protrudes (known as lamellipodium) and then anchors onto the substrate it is crawling on. Then myosin II will contract the tail end so the cell moves.
Describe intermediate filaments.
Primary role is protection from mechanical stress, they are stress absorbers, and at the junctions between cells and with the ECM. no known associated motors.
Their stability is controlled by phosphorylation and they surround the nucleus extending to the cell periphery.
Other functions include cytoarchitecture in the axon, cell migration and movement, and signal transduction.
Basic structure is a coiled coil that forms antiparallel tetramers which 8 tetramers go on to form the intermediate filament.
Examples: keratins, neurofilaments, nuclear lamins.
Describe actin and actin filaments.
Actin monomers bound With ATP which is hydrolyzed to ADP when it is in the filament. It has a polarity with a plus end and a minus end. The filament is helical and actin binding proteins modify the dynamics and higher order assemblies.
Describe tubulin an microtubules.
Microtubules are polymers of alphabeta tubulin. The alpha and beta both bound GDP or GTP, (in this case we only talk about the Beta tubulin on top because the alpha is not going to let the GDP be exchanged.
Microtubules are important for vesicular transport, forming mitotic spindle, in cilia and flagella, basal bodies and centrioles.
Describe microtubule and actin polymerization.
They are both assembled from globular proteins via condensation polymerization reactions.
Nucleotide hydrolysis will lag behind the addition of monomers so an ATP or GTP cap will form at the growing end.
On the minus side, there is no lag and instead, the Monomers are dissociating faster than addition and on the plus side, more is added than lost.
Energy of hydrolysis is not needed for polymerization, instead the nucleotide at the plus end determines the stability.
Dynamics and state of assembly are regulated by actin/microtubule binding proteins,
ACTIN:
nucleation is the rate limiting step, ATP actin is preferentially added to the barbed end.
Microtubules:
Dynamic instability: rapid transitions between growth and shrinking. Sometimes there is loss of the GTP cap and the polymer rapidly shrinks (catastrophe), with rescue the cap is reinstated and rapidly grows.
Describe the various roles of cytoskeletal binding proteins.
Depolymerizing proteins will bind to monomers sequestering them.
They can cap short filaments from a severed long filament and prevent group.
Or they can serve as linkers to form a vast variety of structures.
They can also severe the protein. And stablize or destablize plus or minus ends.
Example tau, a microtubule associated protein, they cross link microtubules together. In Alzheimers, tau forms neurofibrillary tangles.
Example + tip proteins, the bind and track with the + end of a growing microtubule so there can be communication with the periphery. They essentially stabilize it.
Describe primary cilia
Its non motile and most cells have them.
Usually one per cell and they serve as sensory protrusions.
They are structurally different from motile cilia with a lack of a central doublet and dynein arms.
What is the centrosome
Its the microtubule organization center. It contains the centriole pair in addition to pericentriolar material.
It contains a gamma tubulin ring which nucleates the + end of protofilaments and caps the minus ends.
As a result + end is always oriented toward the periphery.
Centrioles duplicate at the beginning of S phase.
Phalloidin
Colchicine
Taxol
Phalloidin - binds and stabilizes actin filaments. Found in the Angel of Death
Colchicine - depolymerizes microtubules
Taxol - binds an stabilizes microtubules, good for cancer because that means it can’t destablize as it does for forming spindle fibers.
What are examples of cell migration?
Neural development - pathfinding for neurons
Chemotaxis- migration of neutrophils to infection sites
-a neutrophil has actin polymerization at the leading edge and myosin II dependent contraction at the other end.
Repair and remolding - migration of cells to repair wounds
Tissue formation
Cancer metastasis.
Describe actin polymerization in regards to movement.
First of all elongation at the barbed ends. And you need alot of actin filaments to generate the force needed. So you nucleate more actin filaments. Or you sever existing ones to create more.
Or form branches from existing filaments.
Arp2/3 complex - it nucleates filaments from the sides of actin, making complex branched structures and is activated by Arp 2/3
-neutrophil migration, wound healing, metastasis, bacterial infections,
How are motor proteins and actin related to mitosis?
Kinesins and dynein are involved in spindle assembly, chromsomal alignment and segregation.
Actin and myosin II are in the contractile ring and cleave the cell.
Describe how the cytoskeleton plays a role in morphogenesis
A sheet of epithelial cells will feature an adhesion belt, the terminal web, + ends are associated at each junction so the terminal web has actin filaments going in both directions. Myosin II makes the belt contract and this causes the folding of the sheet (formation of neural tube)
Generally describe the three classes of motors.
Myosins move along actin filaments, generally to the plus end.
Dyneins move towards the minus end on microtubules
Kinesins move towards the plus end on microtubules.
All three of them are ATPases.
All three of them can only move in one direction
Vesicles and organelles can move on microtubules and actin filaments in two directions so they feature multiple motor proteins.
All three motors turn chemical energy from the binding or hydrolysis of ATP into an intramolecular conformational change which becomes mechanical movement.
Describe the actin motor myosin.
They have two heavy chains with two light chains.
They are generally plus end directed.
The globular head domain contains the ATPase and the heavy chain + light chain (at the base of the head)
The tail is a variable domain, it contains a coil coil for dimerization or to membrane or a vesicle.
Most light chains are camodulin so they can be regulated by calicum. The heavy chain is what binds to actin.
Binding to actin or microtubules accelerate the rate limiting step of releasing inorganic phosphate.
