Cytoskeleton and actin microfilaments Flashcards
cytoskeleton summary:
what is it
what is it needed for
what is it made of
Network of protein filaments that provides structure, support and helps with cell movement. Crucial for cell division, shape maintenance and intracellular transport. Consists of microfilaments, intermediate filaments and microtubules
subunits of microfilaments (macromolecular polymer)
actin
subunits of microtubules
alpha and beta tubulin proteins
form dimers
subunits of intermediate dimers
diverse family of proteins
how can the polymers form higher ordered structures
pack together and cross link via cytoskeleton binding proteins
how are neurotransmitters transported from soma to axon terminals?
motor proteins (kinesin and dynein) move along microtubules
kinesin moves the vesicles anterogradely and dynein moves them retrogradely (back to soma)
cytoskeleton involvement in digestive system and how this maintains polarity across epithelial cells
kinesin and dynein transport vesicles loaded with nutrients and sugars along microtubules: kinesin towards the positive apical surface (lumen side) and dynein towards negative basal surface (blood). actin filaments help to anchor and release vesicles at the membrane
how cells move
Actin microfilaments are responsible for forming protrusions at the front of the cell, known as lamellipodia or filopodia. Actin filaments rapidly polymerize (grow) at the leading edge of the cell, pushing the membrane forward. This creates the force needed for the cell to extend towards the direction it wants to move. leading edge adheres to the extracellular matrix or other cells via integrins and other adhesion molecules, providing traction.
The cell body and rear end contract via actin myosin interactions, pulling the cell forward.
cytoskeleton in muscle contraction
driven by the action of actin microfilaments and myosin that associate with them.
intermediate filaments resist the mechanical stress and tension
microtubules also resist compressive force and generate tracks where substances can be trafficked around the cell
cytoskeleton in cell-cell adhesions
cells linked on cytoplasmic face to cytoskeleton, forces transmitted between cells can be felt by neighbouring cells immediately. forces can be transmitted from cells to extracellular matrix
can respond to environmental changes
what are stress fibres
contractile bundles of actin filaments and associated proteins (eg myosin II). antiparralel to each other. span across cell and connect to focal adhesions. provide tensile strength and rigidity to resist cell deformation. allow cell movement and signal transduction
important in cytokinesis
where are actin microfilaments
underlie membrane
connected to cell-cell and cell-matrix adhesions
structure of actin microfilaments
two strands of helical monomers: globular actin and filamentous actin. Polar: barbed (+) end where polymerisation occurs with greater rate, and pointed (-) end
G actin mechanism
each G actin monomer has a binding site for one molecule of ATP. ATP-bound G actin ha a higher affinity for the polymer at barbed end. ATP hydrolysis weakens the association so at the pointed end, ADP bound G actin monomers are more likely to dissociate.
steady state actin dynamics
rate of addition of monomers = rate of shrinkage
living cells never reach this equilibrium
exponential growth phase of actin filaments
not energetically favourable for individual actin monomers to come together and form a filament = low rate
eventually oligomers form and it is now energetically favourable for monomers to add to the pre-existing filament
exponential growth phase until run out of ATP or actin monomers
filopodia
higher order structure of actin filament
stiff parallel bundles
can send chemical messages/interact with other cells
sense environment
adhere to matrix via integrins
cell movement
at cell membrane
microvilli
lamellipodia
branched (dendritic) network
found at leading edge of cell
cell movement
cortex
gel-like mesh network underlying plasma membrane
protrusion
force of polymerising F actin pushing on membrane
filpodia in neurones
explore and find cells to make contact with
growth cones-actin rich protrusions with long filopodia and enriched in adhesion proteins at the tip
interdigitation
epithelial cells form tight sheets where they pack closely with neighbours. extend their filopodia to make contact with another cell and form adhesions on a large surface area
structure of growth cones
Large parallel bundles of filopodia interspersed within the cross linked dendritic structure of the lamellipodia
role of actin binding proteins
barbed end binding proteins control polymerisation and branching
proteins bind to multiple actin microfilaments and cross link them together
AAP 23 complex
binds to the side of a pre-existing actin micro-filament and encourages/nucleates the growth of a new filament from that position. Gives rise to dendritic structure. Grows off in a 70 degree angle
role of actin bundling proteins
crosslink microfilaments in filopodia
crosslink cortical meshwork
how can some bacteria hijack actin machinery to move around cells
they have proteins on them that acts as actin nucleators
eventually filament punches through the plasma membrane from one cell to another
myosins in cell division
cells form contractile ring structure with lots of actin microfilaments in antiparallel bundles and a high concentration of myosin II
myosins in cellular transport
Provide contractile force by moving along F-actin filaments
Movement along F-actin is polarised: towards barbed end
Transport cargo along a filament
Slide filament relative to organelle or cell membrane
Slide filaments relative to one another
Bundle F-actin filaments together
how do myosins differ
tail domains are variable
actin-binding head domain is highly conserved
monomeric (one head) or dimeric (2 heads)
myosin I
one head
associate with plasma or organelle membranes and bind to actin
involved in endocytosis and membrane trafficking
myosin II
can form large bundles of thick filaments. Myosin-II has two heads per molecule and forms bipolar filaments that can interact with multiple actin filaments simultaneously.
dimeric myosins, eg myosin V
bind to cargo proteins, such as vesicles, and walk along actin filaments, transporting the cargo to different locations within the cell.
mechanism of powerstroke
Actin-binding myosin head meets an actin microfilament and tightly associates with one monomer
Myosin head associates with ATP and undergoes a conformational change that weakens the association with the actin microfilament and it can detach
ATP undergoes hydrolysis which powers a conformational change causing the myosin head group to move to the next actin monomer
The ADP bound myosin can make contact with the next monomer along the microfilament and release the ADP so that the cycle can repeat
non muscle myosin II
myosin with a long tail region and two head groups in the inactive form. When regulatory region in the neck is phosphorylated, causes a conformational change that extends the tail. Now the dimer can form a tetramer. Now have a double headed myosin structure
The bundles are antiparallel to one another so the movement of the myosin heads will slide the filaments relative to one another to generate contractile force
Drives cell division
