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Besidesbinding to actin and phospholipids, profilin also binds to various other intracellularproteins that have domains rich in proline; these proteins can alsohelp to localize profilin to sites that require rapid actin asrembly.As it does with actin monomers, the cell sequesters unpolymerized tubulinsubunits to maintain the subunit pool at a level substantially higher thanthecritical concentration. one molecule of the small protein smnmtibinds to twotubulin heterodimers and prevents their additlon onto the ends of microtubules.
Stathmin thus decreasesthe effective concentration of tubulin subunitsthat are available for polymerization (an action analogous to that of the drugcolchicine). Furthermore, stathmin enhances the rk;hhood that a growingmicrotubule will undergo the catastrophic transition to the shrinkin"g statelPhosphorylation of stathmin inhibits iis binding ro tubulin, and signils thatc.ausestathmin phosphorylation can increase the rate of microtubui=eelongation andsuppress dynamic instability. Cancer cells frequently overexpressstuihmin, and the increased rate of microtubule turnover that results is thought tocontribute to the characteristic change in cell shape associatedwith mahlnanttransformation.severingProteinsRegulatethe Lengthand KineticBehaviorofActinFilamentsand MicrotubulesIn some situations, a cell may break an existing long filament into many smallerfilaments.
This generates a large number of new filament ends: one iongfilament with just one plus end and one minus end might be broken into dozensofshort filaments, each with its own minus end and plus end. under some intracellular conditions, these newly formed ends nucleite filament elongation,andin-this case severing acceleratesthe assembly of new filament structures.underother conditions, severing promotes the depolymerization of old filaments,speeding up the depolymerization rate by tenfbldor more. In addition, severingfilaments changes the physical and mechanical properties of the cytoplasmistiff, large bundles and gels become more fluid when the filaments aresevered.To sever a microtubule, thirteen longitudinal bonds must be broken, oneforeach protofilament. The protein katanin, named after theJapaneseword for"sword," accomplishes-thisdemanding task (Figure16-39). Kaianin is made upof two subunits, a smaller subunit thai hydrolyies Arp and performs theactualsevering, and a larger one that directs katanin to the centrosome.
Kataninreleasesmicrotubules from their attachment to a microtubule organizingcenter,and it is thought to have an important role in the rapid microtub"ule dep"oll,rnerization observed at the poles of spindles during mei,osisand mitosis.It may alsobe involved in microtubule releaseand depolyrnerization in proliferatingcells ininterphase and in postmitotic cells such ai nerr.ons.In contrast to microtubule severing by katanin, which requires ArB thesevering of actin filaments does not requiie an extra energy input.
Mostactin-severing proteins are members of the gekotin superfamity,'whbseseveringactivityis activated by high levels of cytosolic ca2*. Gelsolin has subdomainsthat bindto two different sites on the actin subunit, one exposed on the surfaceof the filament and one that is normally hidden in the longitudinal bond to thenext subunit in the protofilament. 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