Cytoskeleton and Cell Junctions

=large dynamic protein which supports cell shape- defines cellular shape (without CS cell would not have polarity) strength- imparts strength and prevents it from being damaged movement- provides mechanism by which things can move within a cell and by which cells themselves can move

actin filaments- double stranded composed of actin protein subunits regulate cell shape and locomotion microtubules intermediate filaments (IF)

Actin filaments enable microvilli formation (important for nutrient absorption) Actin also connects to cell junctions to maintain a physical barrier Intermediate filaments (IF) anchor across the cell providing structure and strength via cell junctions called desmosomes Microtubules run from basal to apical surfaces providing a intracellular transport network (polarity- have + and - end)

refers to asymmetry; shape, structure, organisation cell is not uniform

IFs held together by non covalent interactions eg h bonds, electrostatic single protofilaments are thermally unstable as one break doesnt require much energy (very weak) multiple protofilaments are thermally stable (strong) breaking whole filament requires lots of energy to break bond

8nm diameter, thinnest filament regulate cell shape and locomotion F actin=filament G-actin= globular (monomer of which F actin is formed) 2 polymer chains form helix can be found as linear bundles, 2D networks and 3D gels has a large cleft in centre which binds ATP G-actin subunits all point same way- polarity (have + end and - end)

first step in formation of a new structure via self assembly 2 ATP G actin subunits bind to each other weakly when 3 ATP G actin subunits form a trimer it acts as a nucleus from which a large actin filament can form

nucleation (lag phase)- actin subunits not yet in filaments elongation (growth phase)- growing actin filament (once trimer has formed) steady state (equilibrium phase)- actin filaments with subunits coming on and off Cc- critical concentration (steady state)- G actin monomers and F actin are in equilibrium rate of G actin addition and dissociation is equal at each end of actin chain Gactin>Cc favours addition Gactin<Cc favour dissociation Cc is determined by 2 constants Kon= rate of addition Koff= rate of dissociation Cc= Koff/Kon

subunits are added faster at + end and dissociate faster at - end due to differences in Cc causes + end to grow and - end to shrink overall length of F actin remains constant - remains in equilibrium essential for cell motility and alterations in cell shape

F actin can form interactions with motor proteins eg myosin, kinesin, dynein assists in movement myosin binds to actin ATP hydrolysation releases energy mysosin pulls itself along F actin molecule results in movement (muscle contraction) myosin discovered in skeletal muscle, arranged in a way that myosin heads oppose each other and can pull actin filaments closer to each other in skeletal muscle, treadmilling is prevented by binding proteins such as tropomudulin

long hollow cylinders of globular protein tubulin with central lumen regulate cell transport largest filament each protofilament formed of repeated αβ tubulin heterodimers 13 longitdinally repeating units- long strands called protofilaments containing hollow lumen helical structure vertical interactions- α- and β-proteins lateral interactions- α/ α and β/ β microtubules very stiff polarity- β-tubulin exposed at the (+) end α-tubulin exposed at the (-) end

nucleation- within microtubule organising centres MTOC called centrosome (-) end remains anchored to centrosome + grows out of centrosome (+) end first

two features -pair of centrioles -pericentriolar material organised structures consisting of 9 sets of triplet microtubules orientated at 90 degrees to each other - end anchored and + end pointing outwards

amorphous material - disorgansies area of proteins contains gamma tubulin ring complex ( gamma turc) consists of multiple copies of y tubulin complexed with other proteins y turc is specific site for nucleation for microtubules

have very short lifespan polymerisatoon kinetics are similar to that of F actin Cc is lower at + end and higher at - end so + end grows and - end shrinks (treadmilling) dynamic instability- causes by premature hydrolysing of gtp in terminal heterodimer as filament is growing, monomers have gtp, hydrolysis of gtp guarentees to add next monomer, if hydrolysis occurs before next monomer is added, causes shrinking back effects

responsible for movement along microtubule kinesin- moves towards +ve end of microtubules (anterograde- away from centre) dynein- moves towards -ve end of microtubule (retrograde- towards centre)

starts with microtubule surface and kinesin molecule lagging head is ATP bound- strongly associated with MT leading head is ADP bound- weakly associated with MT hydrolysis of ATP causes lagging head to dissociate from MT leading head binds to ATP, causes conformational change (still bound to surface of MT) lagging heads move forwards and binds further down MT hand over hand mechanism how cargo gets transported along MTs (dyenin similar mechanism but move golgi vesicles)

provide mechanical strength (10nm thick) multiple types composed of different subunits much greater tensile strength than others non polar- symmetrical not associated motor proteins- not involved in cellular movement great heterogeneity (lots of types) within IF

alpha helical region of monomer forms coiled coil dimer staggered tetramer of two coiled coil dimers lateral association of 8 tetramers addition of 8 tetramers to growing filament provides lots of strength eg in nuclear lamina

multicellular organised structures can withstand and respond to external cues cells must link to eachother and to extracellular matrix (ECM) categories- epithelial, muscle, nervous, connnective

sheets of cells- line surfaces of bod ecm is present as a very thin sheet called basal lamina

these cells produce ECM and are sparsely populated within dense matrix

anchoring junctions- anchor cytoskeleton between cells or between cells and ECM occluding junctions -prevents passage of ions and small molecules between cells. typically tight junctions in vertebrates communicating junctions- direct connections between cytoplasm of two cells- gap junctions

depend on transmembrane (across membrane) adhesion proteins -one end binds to cytoskeleton -other ends binds to something extracellular these cytoskeletal linked transmembrane proteins belong to two superfamilies cadherins- cell cell attachment integrins- cell matrix attachment