Catastrophin

Catastrophin (Catastrophe-related protein) is a term use to describe proteins that are associated with the disassembly of microtubules. Catastrophins affect microtubule shortening, a process known as microtubule catastrophe.[1]

Overview of Microtubule Dynamics

Microtubules are polymers of tubulin subunits arranged in cylindrical tubes. 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 the microtubule.[2] However, this GDP can be displaced by GTP. Beta-tubulin bounded to GTP are describe as having a GTP-cap that enables stable growth.[3]

Microtubules exist either in either a stable or unstable state. The unstable form of a microtubule is often found in cells that are undergoing rapid changes such as mitosis.[1] The unstable form exists in a state of dynamic instability where the filaments grow and shrink seemingly randomly. A mechanistic understanding of what causes microtubules to shrink is still being developed.[4]

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.[5]

Catastrophins that Increase Catastrophe

Oncoprotein 18/Stathmin has been shown to increase the frequency of catastrophe.[5]

The Kinesin-related protein XKCM1 stimulates catastrophes in Xenopus microtubules.[1]

The Kinesin-Related Protein 13 MCAK increases the frequency of catastrophe without affecting the promotion of microtubule growth.[6]

Catastrophins that Inhibit Catastrophe

Doublecortin (DCX) shows an ability to inhibit catastrophe without affecting the microtubule growth rate[5]

Xenopus Microtubule Protein 215 (XMAP215) has been implicated in inhibiting catastrophe.[1]

Mechanisms of Catastrophins

Some catastrophins affect catastrophe by binding to the ends of microtubules and promoting the dissociation of tubulin dimers.[7]

Different mathematical models of microtubule development are being developed to take into account in vitro and in vivo observations.[5] 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 microtubules.[8]

See also

References
  1. Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter (2002-01-01). "Mitosis". Cite journal requires |journal= (help)
  2. Lodish, Harvey; Berk, Arnold; Zipursky, S. Lawrence; Matsudaira, Paul; Baltimore, David; Darnell, James (2000-01-01). "Microtubule Structures". Cite journal requires |journal= (help)
  3. Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter (2002-01-01). "The Self-Assembly and Dynamic Structure of Cytoskeletal Filaments". Cite journal requires |journal= (help)
  4. Lodish, Harvey; Berk, Arnold; Zipursky, S. Lawrence; Matsudaira, Paul; Baltimore, David; Darnell, James (2000-01-01). "Microtubule Dynamics and Associated Proteins". Cite journal requires |journal= (help)
  5. Bowne-Anderson, Hugo; Hibbel, Anneke; Howard, Jonathon (2015-12-01). "Regulation of Microtubule Growth and Catastrophe: Unifying Theory and Experiment". Trends in Cell Biology. 25 (12): 769–779. doi:10.1016/j.tcb.2015.08.009. ISSN 1879-3088. PMC 4783267. PMID 26616192.
  6. Hunter, Andrew W.; Caplow, Michael; Coy, David L.; Hancock, William O.; Diez, Stefan; Wordeman, Linda; Howard, Jonathon (2003-02-01). "The Kinesin-Related Protein MCAK Is a Microtubule Depolymerase that Forms an ATP-Hydrolyzing Complex at Microtubule Ends". Molecular Cell. 11 (2): 445–457. doi:10.1016/S1097-2765(03)00049-2. ISSN 1097-2765. PMC 6468321.
  7. Helenius, Jonne; Brouhard, Gary; Kalaidzidis, Yannis; Diez, Stefan; Howard, Jonathon (2006-05-04). "The depolymerizing kinesin MCAK uses lattice diffusion to rapidly target microtubule ends". Nature. 441 (7089): 115–119. Bibcode:2006Natur.441..115H. CiteSeerX 10.1.1.392.1014. doi:10.1038/nature04736. ISSN 0028-0836. PMID 16672973.
  8. Moriwaki, Takashi; Goshima, Gohta (2016-11-07). "Five factors can reconstitute all three phases of microtubule polymerization dynamics". J Cell Biol. 215 (3): 357–368. doi:10.1083/jcb.201604118. ISSN 0021-9525. PMC 5100292. PMID 27799364.


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