Movement Flashcards
What is the primary function of the cytoskeleton elements (micro- and macrofilament and intermediatery filaments)
is to hold a particular cell in a particular shape
There are multiple different cell shapes across cells and organisms
Why are cell different shapes
So they can relate to their specilist function
E.g. Microvilli to increase surface area for absorption
Heavily filamented structure of fibroblast use for structural framework in animals cells
Where do all microtubules start from
The centrizone - microtubule organising centre found next to the nucleus
What is the cytoskeleton
A highly dynamic netweok of three main filaments and their associated protiens, that can response and change rapidly to specific singals
Name some key biological features of actin
- Highly conserved - same across 80% of eukaryotes and well as being found it prokaryotes too
- Highly abundant within cells (1-5% of total protein is actin)
- Ubiquitous - exists within every cell within the body
- Can bind to ATP and hydrolyse it (ATPase)
What is the monomer of Actin
And how does it shape link to its function
G-actin = Globular actin (375 amino acids)
It is heart shaped (has a little cleft used for binding ATP), which direct the polymerisation of the polymer from the monomer, in a polarised manner
What is the polymer of Actin
F-Actin = Filamentous actin (the thin muscle filaments), which form microfilaments
In is the linear monomer of G-Actin
How is the Filamentous Actin structured
- Two linear polymers of G-actin which wrap around another (around 14 units long)
- The actin filaments are polarised due to the heart-shaped G-Actin monomer, leading to a minus end on one side of the string and a positive end on the other (this is not a charge, this is where new monomers are added)
- It doesn’t require any other co-factors to form this shape
What are the 3 steps in F-actin assembly
- Nucleation (RDS) 3 G-Actin monomers (nucleation trimer) together to nucleate the assembly
- Elongation: rapid addition of G-Actin monomers on the plus end (exponentation growth)
- Steady state: adding and subtrating G-Actin at both ends
What is tredmilling in terms of the synthesis of Actin filaments
The movement of the nucleation trimer from the positive to negative end of the actin filament due to adding G-Actin at the positive end and removing int at the negative end
As this happens ATP is hydrolysed forming ADP leading to you needing a far greater amount of actin at the negative end for G-Actin to be added
How does synthesis of F-Actin relate to the shape of cells
Because F-Actin filaments can only be synthesised in one direction
Therefore if a singal such as a nutrient source occured in the opposite direction of those filaments, disassembly of filaments and rapid diffusion of subunits. Then reassembly of filamentd at a new site occur, alterining the direction of thr cell
The diversity of cellular functions achieved by actin is mostly due to
These in turn are regulated by what?
Of the diversity of Actin Binding Proteins (ABPs) which associate with actin (both eith G-Actin and F-Actin)
ABPs are regulated by signalling molecules, which impacts on actin and causes structural changes and motility changes within the cell
e.g. promotion of assembly of actin by increasing the G-Actin-ATP pool or ABPs which bind to the filament to stabilise it
Give an example of the importance of actin polymerisation
When actin polymerisation is hijacked in a eukaryote by bacteria which results in food poisoning
Bacteria invades a cell and utilises the hosts F-Actin self assembly mechanisms to get jet-propelled through the cell
What are some features of microtubules
are minute tubes, found in all cells (ubiquitous)
They are polymers built from the protein tubulin and each ‘brick’, has two types of tubulin (Alpha & Beta) forming a heterodimer
Both monomers can bind to GTP, but only the beta form can hydrolyse it to GDP
The orientation is such that the addition is at the beta end, and the alpha is the minus end
Which key cell structure is composed of microtubules
The Mitotic Spindle
Explain the term Treadmilling in terms of Microtubule assembly
Microtubules also have intrinsic polarity, that preferentially adds their subunits at one end
This requires a lower critical concentration of unincorporated heterodimers for the addition
The adding of heterodimers at the beta end and the removal at the positive end leads to the treadmil affect
What is another feature which is unique to microtubule synthesis
Dynamic instability arises from the alteration between two states known as catastrophe and rescue, during which the microtubule either shrinks of grows, from its plus end
Whether the microtubule is in a catastrophic phase or a rescue phase depends on what nucleotide form is present at the plus end. Depending on the speed of addition of the subunits at the beta end, depends on whether the hydrolysis is faster or slower than the addition
If addition at this end is slow and thus GTP hydrolysis occurs at same rate or faster, GDP-bound beta-tubulin becomes exposed and the ends peel and curve off ‘catastrophe’ and the microtubule rapidly shrinks
What two substrates can affect Dynamic instability
MAPs - Microtubule associated proteins can encorage stabilisation
Catastrophe factors (Kinesin 13) - encorages detabilisation and increases frequency of catastrophes
Given some key characteritics of Myosin II
It is a double headed chain (this houses ATPases)
They have two types (essential and regulatory) of light chains at their neck region, which determines how the head region behaves
The tail is comprised of a heavy chains which coil together with other ones
There are mutiple head at both ends
In skeletal muscle, how are the actin and myosin filaments arranged?
Alternating layers on thick (myosin) and thin (actin) filaments
This form the sacromere
During a contraction, the myosin will move towards the plus end of the actin filament (howver no more G-Actin is added to the F-Actin at thhis stage
Describe the Actin-Myosin II Cross Bridge Cycle
- The Myosin head (where the ATPase is) binds to the actin filament (remember myosin is double-headed)
It is in a rigour state as there is ADP bound at this point. In an actively contracting muscle, this state is very short-lived, being rapidly terminated by the binding of ATP on the back of the myosin head - This causes a change in the conformation of the actin-binding site, reducing the affinity of head for actin
- The ATP is hydrolysed to ADP and pi, still being bound to the protein. This allows the head to cock, resulting in a displacement along the filament (towards + end)
- The Pi is released allowing binding of myosin head to a new actin-binding site. This triggers a power stroke, where the head returns to its original conformation from the cocked position. The bound ADP is lost
- A new cycle starts
Where are the Z disks located in the Sliding Filament Mechanism
Where the plus ends of the actin filaments are
Where are the I and A bands located on the sacromere
A band - Entire length of myosin, doesnt change in length
I band - part of the sacromere where there is just actin, this get shorter during a contraction
There are two types of Myosin V molecules
Kinesins - move in the Plus end direction (anterograde)
Dyneins - move in the minus end direction (retrograde)
Basically depends on the direction of movement along the Microtubule-based Motors. They can pick up the same organelle or cargo
What is the structure of Kinesin like
similar to Myosin V, it has a head region, where it will associated the the microtubles, containing ATPases
It has a long heavy heavy chain region, which is a homodimer
Two light chains at the end which are used to associate with cargo
Just like Myosin V, Kinesin is a processive Motor
Explain how Kinesin 1 moves along microtubules
- The forward motor binds to B-tubulin, releasing ADP
- The forward head then binds
- There is a conformational change in the neck linker, causing the rear head to swing forward
- New forward head releases ADP, trailing head hydrolyses ATP and releases Pi
Describe the structure of Dynein
It has two circular heads, which rotate as ATP bind and ADP unbinds
At its n-terminus, there is the microtubule binding domain
At its c-terminus there is the binding domain, where it will bind to dynactin
There are lots of extra molecules associated with dynein structure, which means there isn’t a superfamily
Dynein is also found within the axoneme of structures
Name a new examples:
Flagella (and cillia) : tails of sperm
There are composite microtubule structures which are held together by arms
These arms are made of primarily axonemal dynein holding at its c-terminus
How does dynein in Axonome allow for behind, hence whole cell motility
Dynein will hold on to microtububles at its c-terminus
Activation of dynein bend the microtuble doublets
This allows the sperm tail for example to wiggle
