Mammals have

actin isoforms -

muscle-specific

actins and 2 non-muscle

actin for cell cortex and leading edges of migrating cells, and stress fibres are made up of

gamma

actin.

Actin filaments are polymers of (globular/fibrous)

actin monomers. There are two types of actin structures

actin when it forms a

3D structure or

actin when it forms a filaments. Unlike microtubules, actin filaments use

hydrolysis. The filaments are two parallel helical strands that exert polarity. Monomers are preferentially added to the

end of the actin filament. After binding to this end, ATP is hydrolysed and a phosphate group is slowly released. Actin molecule undergoes a conformational change, which causes the different kinetics at the plus and minus ends.

Many accessory proteins bind to actin to regulate its structure and dynamics. There are two types of proteins that accelerate actin treadmilling.

binds to the minus-end causing a kink in the filament, which causes sections of it to break off and allow the presence of several minus-ends. This releases more

bound actin monomers.

enhances the exchange of ADP back to ATP by opening up the ATP-binding cleft. There are also other proteins that bind to the very ends of the filaments, known as

proteins, which block filament assembly and dissassembly.

binds and blocks the plus-ends of the filaments. While

binds and blocks the minus-ends, which allows the filaments to stabilise in muscle.

There are several drugs that can be used to inhibit actin polymerisation in vivo, such as

which binds and blocks plus-ends, preventing addition of further subunits.

binds and sequesters G-actin.

Actin Nucleating Proteins are activated by the

family of GTPases recruited to plasma membrane:

, Rac and

. Formins nucleate (long/short branched/unbranched)

filaments. It is activated by the binding of Rho-GTP. These types of filaments are in

of muscle and stress fibres.

is a 7 subunit complex, in which 2 subunits are actin-related. This complex creates

on

actin filaments. This complex requires the binding of a regulatory protein, known as

. These regulatory proteins are activated by the small GTPases

or Rac.

Fimbrin and

are able to cross-link

microfilaments, creating

filament bundles.

and Filamin create looser meshworks and networks. Adaptor proteins attach actin filaments to membranes. One classic example is

which are membrane-spanning proteins that can attach to cell interior and

as well. This allows the membrane to fold itself around these to change shape of the cell.

Actin in a migrating cell can be stained using fluorescently-labelled

. A migrating cell has a front and back. At front, is the

, towards the rear of the cell are

- contractile filaments to help push cell forwards through contractions. The cell moves forward using

adhesions. As new adhesion is made, stress fibres contract and push cell forward. Rho,

and Cdc42 work together to co-ordinate cell migration. They are activated by extracellular signals that activate these GTPases at the plasma membrane.

GTPase establishes cell polarity and formation of the leading edge of the migrating cell. WASp gets activated to stimulate

to form branched actin filaments, forming the lamellipodium. At the same time, Cdc42 activates proteins, including

, which reorganise microtubules. Towards the rear of the cell, stress fibres are formed by

GTPase.

Intermediate filaments have a conserved structure with a central

domain that promotes dimerisation. They are fairly uniform in length at around 300aa, but have varying sizes of

head and

tails. Their structure allows them to not only dimerise, but to form a higher order of multimers ending up in a rope-like structure. They associate to form a dimer first, which can further associate to form a

of two coiled-coil dimers. Further more, two of these can pack together in a (parallel/anti-parallel)

fashion.

tetramers twist together into a rope-like structure.

Intermediate filaments are non-polar and much

stable than actin and microtubules. They bend (barely/easily)

, however are (easy/difficult)

to break due to several interactions of intertwined molecules. Intermediate filaments provide the cells with tensile strength and resistance to

B-type lamins -

- are thought to be expressed in cell from (adulthood/early development)

and are there to provide all nuclei with structural support.

lamins - A and C - are expressed (later/earlier)

in development and thought to help cells specialise possibly by regulating gene expression patterns.

Keratins are much more varied and have about 54 genes encoding them. They are found in

cells, such as in the gut, skin and nails. They are formed from (homo/hetero)

dimers of acidic and basic chains.

bonds cross-link the filaments forming very strong networks.

forms 14% of residues in the hair keratins. Keratins strengthen epithelia through

. Neurofilaments have

different types according to size and are encoded by distinct genes NF-L

and NF-H. These provide tensile strength to

. Neurofilaments also form cross-links, it is thought that longer neurofilaments have domains for cross-linking between each other.