Cytoskeleton summary Flashcards

Question

Actin treadmilling allows

Answer 1

Movement Length is constant but polymer moves Rate of loss = rate of addition

Answer 2

More flexible, but much shorter - accessory proteins have to link

Answer 3

``` Straight = formin Branched = Arp2/3 ```

Answer 4

``` Microtubules = long range Actin = short range ```

Answer 5

Nucleation (lag phase) | Proteins catalyse

Answer 6

Highly conserved during eukaryotic evolution Whereas accessory proteins have not

Answer 7

The filaments interact with so many proteins that structure variability is not possible Mutations in the shape of the filament might be beneficial for one protein but not for another So proteins are varied instead

Answer 8

Cell migration - lamellipodium

Answer 9

The extracellular matrix to provide traction

Answer 10

Mechanical stress - shorter than mt and actin but very tough In the nucleus: nuclear lamins protect DNA In the nerve cells: neurofilaments In the connective tissues: vimentin Epithelia: keratins

Answer 11

Severeal human genetic diseases e.g. epidermolysis bullosa simplex (keratin mutation) e. g. Lou Gehrig's disease (neurofilament mutation - abnormal assembly of neurofilaments in motor neuron cell bodies and axons results in muscle atrophy as neurofilament gene expression directly affects axonal diameter, and how fast a signal can travel) e. g. Desmin (vimentin family) lacking mice have misaligned muscle fibres all diseases characterised by cell rupture as a consequence of mechanical trauma

Answer 12

Cytoskeleton Microtubule drugs: Taxol - binds MTs, stabilises Colchicine - binds subs, prevents assembly Vinbastine - binds subs, prevents assembly Nocodazole - binds subs, prevents assembly ``` Actin drugs: Phalloidin - binds subs, stabilises Cytochalasin - caps +ends Swinholide - severs filaments Lantruculin - binds subs, prevents assembly ```

Answer 13

Binds to the face of the actin monomer opposite the ATP binding cleft This blocks the side of the monomer that associates with the minus end of actin and leaves exposed only the plus end binding site Profilin-actin complex adds to the filament Addition causes a conformational change in actin that causes profilin to dissociate Profilin activity is heavily regulated - profilin phosphorylation and profilin binding to inositol phospholipids Profilin is localised at the cytosolic face of the plasma membrane because it binds to acidic phospholipids there - this enables extracellular signals to activate profilin quickly - like lamellipodia and filopodia Profilin competes with Thymosin, which binds actin and stops it from polymerizing

Answer 14

Binds to tubulin heterodimers and prevents their addition to a microtubule Stathmin both decreases the effective concentration of available tubulin subunits and makes a catastrophe more likely Phosphorylation of stathmin inhibits its binding to tubulin and increases microtubule growth and decreases likelihood of catastrophe Cancer cells frequently over express stathmin - the increased microtubule growth produces the characteristic malignant cell shape

Answer 15

Japanese word for 'sword' Severs the 13 bonds of each protofilament Katanin is made of two subuntis - one severs by hydrolysing ATP, the other directs Katanin to the centrosome Katanin releases microtubules from the MTOC and causes rapid microtubule depolymerisation of the spindle during mitosis and meiosis

Answer 16

Actin severing proteins Requires high levels of cytosolic Ca2+ NOT ATP Gelsolin has two subunits that bind to two different sites on actin - one on the filament surface and one between one actin subunit and the next To do this, gelsolin waits for a thermal fluctuation that creates a small gap between neighbouring actin subunits in the filament, then places its subdomain into the gap, breaking the filament

Answer 17

Microtubule associated proteins Can bind along the sides of microtubules and stabilize or destabilize them They do this by either raising or lowering the free energy of the polymer state by binding Tau and MAP2 bundle microtubules - 2 domains: one binds along the microtubule and the other sticks out to contact other MAPs MAPs are controlled by phosphorylation - e.g. protein kinases control MAPs during the formation of the mitotic spindle Tau - binds to filaments and regulates transport of organelles, at very high concentrations Tau forms helices with itself (neurofibrillary tangles, Alzheimers)

Answer 18

Tropomyosin: Stabilises actin Binds along the sides of 7 actin filaments simultaneously Prevents the actin filament from interacting with other proteins - e.g. binding of Ca2+ regulates tropomyosin and is integral to muscle contraction Cofilin: Destabilises actin Binds to actin in both filament and monomeric forms Cofilin binds along the filament, causing tight twisting and weakening the filament making it more easily broken by thermal motions Also causes ADP actin to be more easily lost from the minus end Cofilin binds preferentially to ADP actin so newer filaments (with more ATP bound actin) are resistant to cofilin, so older filaments preferentially dismantled Cofilin is essential for polarised growth of the actin network associated with crawling

Answer 19

Influence rates of growth and catastrophe Kinesin13 family Bind to microtubule ends and pry protofilaments apart, lowering the Ea MAPs oppose catastrophe factors - e.g XMAP215 stabilize free microtubule ends and inhibit shrinking Phosphorylation of XMAP during mitosis inhibits activity and essential for the formation of the mitotic spindle

Answer 20

Some IFs can bundle by self association (NF-M and NF-H bind with their C terminus) Filaggrin bundles Keratin filaments Plectrin cross links IFs to microtubules, actin and the plasma membrane Mutations in plectrin cause epidermolysis bullosa, muscular dystrophy and neurodegeneration - very essential protein!