User:Tomhoang18/sandbox/Week4Assignment

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Catastrophin, or KIF2, is a microtubal motor protein which causes destabilization, i.e. increases dynamic instability, of the microtubule plus (+) end. It is specifically a kinesin-like protein with a motor domain situated in the middle portion of its heavy chain. Contrary to probable belief, the catas- prefix is related to the cata- in catabolism while the -troph- is related to the -troph- in atrophy. The -in is merely a suffix many proteins share.

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Catastrophin (Catastrophe-related proteins)
Catastrophin is a term use to describe proteins that are associated with microtubule's disassembly. Catastrophins affect microtubule shortening, a process known as microtubule catastrophe.

Overview of Microtubule Dyanmics
Microtubules are polymer of tubulin subunits arranged in cylindrical tube. The subunit is made up of alpha and beta tubulin. GTP binds to alpha tubulin irreversibly. Beta tubulin binds GTP and hydrolyzes to GDP. It is the GDP bound to beta-tubulin that regulates the growth or disassembly of microtubule. However, this GDP can be displaced by GTP. Beta-tubulin bounded to GTP are describe as having a GTP-cap that enables stable growth.

Microtubules exist either as either stable or unstable state. The unstable form of microtubule is often found in cells that are undergoing rapid change such as mitosis .The unstable form exists in a state dynamic instability whereas the filament grow and shrink seemingly randomly. A mechanistic understanding of what causes microtubule to shrink is still being developed.

Model of Catastrophe
One model proposes that loss of the GTP-cap causes the GDP-containing protofilaments to shrink. Based on this GTP-cap model, catastrophe happens randomly. The model proposes that an increase in microtubule growth will correlate with a decrease in random catastrophe frequency or vice versa. The discovery of microtubule-associated proteins that change the rate of catastrophe while not impacting the rate of microtubule growth challenges this model of stochastic growth and shrinkage.

Catastrophins that Increase Catastrophe
Oncoprotein 18/Stathmin has been shown to increase the frequency of catastrophe.

The Kinesin-related protein XKCM1 stimulates catastrophes in Xenopus microtubule

The Kinesin-Related Protein 13 MCAK increases the frequency of catastrophe without affecting promoting microtubule growth.

Catastrophins that Inhibit Catastrophe
Doublecortin (DCX) shows an ability to inhibit catastrophe without affecting the microtubule growth rate

Xenopus Microtubule Protein 215 (XMAP215) has been implicated in inhibiting catastrophe.

Mechanisms of Catastrophins
Some catastrophins affect catastrophe by binding to the ends of microtubule and promoting the dissociation of tubulin dimers.

Different mathematical models of microtubule development are being developed to take into account in vitro and in vivo observations. Meanwhile, there are new in vitro models of microtubule polymerization dynamics, of which catastrophins take a part in, being tested to emulate in vivo behaviors of microtubule.