Catastrophin

Last updated October 23, 2022

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]

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 described as having a GTP-cap that enables stable growth.^[3]

Microtubules exist 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]

Increases

Oncoprotein 18/Stathmin has been shown to increase the frequency of catastrophe.^[5] Oncoprotein 18 (Op18) is a cytosolic protein that are found in abundance in either benign or malignant tumor site: through the complex timing of phosphorylation, this biomolecule regulates the depolymerization of microtubules.^[6] It has four sites of phosphorylation characterized by serine residues and are associated with cyclin-dependent protein kinases (CDKs): Ser16, Ser25, Ser38 and Ser63.^[7]^[8] There are two different models that are in contention regarding the destabilization of microtubules due to Op18: the inhibition of tubulin dimer formation or a catastrophe phenomena. ^[7]

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.^[9]

Decreases

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]

Mechanism

Some catastrophins affect catastrophe by binding to the ends of microtubules and promoting the dissociation of tubulin dimers.^[10]

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.^[11]

Related Research Articles

Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 and 15 nm. They are formed by the polymerization of a dimer of two globular proteins, alpha and beta tubulin into protofilaments that can then associate laterally to form a hollow tube, the microtubule. The most common form of a microtubule consists of 13 protofilaments in the tubular arrangement.

<span class="mw-page-title-main">Spindle apparatus</span> Feature of biological cell structure

In cell biology, the spindle apparatus refers to the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a process that produces genetically identical daughter cells, or the meiotic spindle during meiosis, a process that produces gametes with half the number of chromosomes of the parent cell.

Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytoskeleton. Microtubules function in many essential cellular processes, including mitosis. Tubulin-binding drugs kill cancerous cells by inhibiting microtubule dynamics, which are required for DNA segregation and therefore cell division.

A kinesin is a protein belonging to a class of motor proteins found in eukaryotic cells.

<span class="mw-page-title-main">Kinetochore</span> Protein complex that allows microtubules to attach to chromosomes during cell division

A kinetochore is a disc-shaped protein structure associated with duplicated chromatids in eukaryotic cells where the spindle fibers attach during cell division to pull sister chromatids apart. The kinetochore assembles on the centromere and links the chromosome to microtubule polymers from the mitotic spindle during mitosis and meiosis. The term kinetochore was first used in a footnote in a 1934 Cytology book by Lester W. Sharp and commonly accepted in 1936. Sharp's footnote reads: "The convenient term kinetochore has been suggested to the author by J. A. Moore", likely referring to John Alexander Moore who had joined Columbia University as a freshman in 1932.

In cell biology, microtubule-associated proteins (MAPs) are proteins that interact with the microtubules of the cellular cytoskeleton. MAPs are integral to: the stability of the cell and its internal structures and the transport of components within the cell

Motor proteins are a class of molecular motors that can move along the cytoplasm of animal cells. They convert chemical energy into mechanical work by the hydrolysis of ATP. Flagellar rotation, however, is powered by a proton pump.

Stathmin, also known as metablastin and oncoprotein 18 is a protein that in humans is encoded by the STMN1 gene.

Treadmilling is a phenomenon observed in many cellular cytoskeletal filaments, especially in actin filaments and microtubules. It occurs when one end of a filament grows in length while the other end shrinks resulting in a section of filament seemingly "moving" across a stratum or the cytosol. This is due to the constant removal of the protein subunits from these filaments at one end of the filament while protein subunits are constantly added at the other end. Treadmilling was discovered by Wegner, who defined the thermodynamic and kinetic constraints. Wegner recognized that: “The equilibrium constant (K) for association of a monomer with a polymer is the same at both ends, since the addition of a monomer to each end leads to the same polymer.”; a simple reversible polymer can’t treadmill; ATP hydrolysis is required. GTP is hydrolyzed for microtubule treadmilling.

Aurora kinase B is a protein that functions in the attachment of the mitotic spindle to the centromere.

Microtubule-associated protein 4 is a protein that in humans is encoded by the MAP4 gene.

Tubulin alpha-4A chain is a protein that in humans is encoded by the TUBA4A gene.

Tubulin alpha-1A chain is a protein that in humans is encoded by the TUBA1A gene.

Targeting protein for Xklp2 is a protein that in humans is encoded by the TPX2 gene. It is one of the many spindle assembly factors that play a key role in inducing microtubule assembly and growth during M phase.

Kinesin-like protein KIF11 is a molecular motor protein that is essential in mitosis. In humans it is coded for by the gene KIF11. Kinesin-like protein KIF11 is a member of the kinesin superfamily, which are nanomotors that move along microtubule tracks in the cell. Named from studies in the early days of discovery, it is also known as Kinesin-5, or as BimC, Eg5 or N-2, based on the founding members of this kinesin family.

Kinesin family member 15 is a protein that in humans is encoded by the KIF15 gene.

The XMAP215/Dis1 family is a highly conserved group of microtubule-associated proteins (MAPs) in eukaryotic organisms. These proteins are unique MAPs because they primarily interact with the growing-end (plus-end) of microtubules. This special property classifies this protein family as plus-end tracking proteins (+TIPs).

Neurotubules are microtubules found in neurons in nervous tissues. Along with neurofilaments and microfilaments, they form the cytoskeleton of neurons. Neurotubules are undivided hollow cylinders that are made up of tubulin protein polymers and arrays parallel to the plasma membrane in neurons. Neurotubules have an outer diameter of about 23 nm and an inner diameter, also known as the central core, of about 12 nm. The wall of the neurotubules is about 5 nm in width. There is a non-opaque clear zone surrounding the neurotubule and it is about 40 nm in diameter. Like microtubules, neurotubules are greatly dynamic and the length of them can be adjusted by polymerization and depolymerization of tubulin.

Edwin W. Taylor is an adjunct professor of cell and developmental biology at Northwestern University. He was elected to the National Academy of Sciences in 2001. Taylor received a BA in physics and chemistry from the University of Toronto in 1952; an MSc in physical chemistry from McMaster University in 1955, and a PhD in biophysics from the University of Chicago in 1957. In 2001 Taylor was elected to the National Academy of Scineces in Cellular and Developmental Biology and Biochemistry.

J. Richard McIntosh is a Distinguished Professor Emeritus in Molecular, Cellular, and Developmental Biology at the University of Colorado Boulder. McIntosh first graduated from Harvard with a BA in Physics in 1961, and again with a Ph.D. in Biophysics in 1968. He began his teaching career at Harvard but has spent most of his career at the University of Colorado Boulder. At the University of Colorado Boulder, McIntosh taught biology courses at both the undergraduate and graduate levels. Additionally, he created an undergraduate course in the biology of cancer towards the last several years of his teaching career. McIntosh's research career looks at a variety of things, including different parts of mitosis, microtubules, and motor proteins.

References

1 2 3 4 Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (January 2002). "Mitosis". Molecular Biology of the Cell (4th ed.). New York: Garland Science. ISBN 978-0-7167-3706-3.
↑ Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J (January 2000). "Microtubule Structures". Molecular Cell Biology (4th ed.). ISBN 978-0-7167-4366-8.
↑ Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (January 2002). "The Self-Assembly and Dynamic Structure of Cytoskeletal Filaments". Molecular Biology of the Cell (4th ed.). New York: Garland Science. ISBN 978-0-7167-3706-3.
↑ Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J (January 2000). "Microtubule Dynamics and Associated Proteins". Molecular Biology of the Cell (4th ed.). New York: Garland Science. ISBN 978-0-7167-3706-3.
1 2 3 4 Bowne-Anderson H, Hibbel A, Howard J (December 2015). "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. PMC 4783267 . PMID 26616192.
↑ Marklund U, Larsson N, Gradin HM, Brattsand G, Gullberg M (October 1996). "Oncoprotein 18 is a phosphorylation-responsive regulator of microtubule dynamics". The EMBO Journal. 15 (19): 5290–5298. doi:10.1002/j.1460-2075.1996.tb00914.x. PMC 452273 . PMID 8895574.
1 2 Brattsand G (August 2000). "Correlation of oncoprotein 18/stathmin expression in human breast cancer with established prognostic factors". British Journal of Cancer. 83 (3): 311–318. doi:10.1054/bjoc.2000.1264. PMC 2374559 . PMID 10917544.
↑ Larsson N, Marklund U, Gradin HM, Brattsand G, Gullberg M (September 1997). "Control of microtubule dynamics by oncoprotein 18: dissection of the regulatory role of multisite phosphorylation during mitosis". Molecular and Cellular Biology. 17 (9): 5530–5539. doi:10.1128/MCB.17.9.5530. PMC 232401 . PMID 9271428.
↑ Hunter AW, Caplow M, Coy DL, Hancock WO, Diez S, Wordeman L, Howard J (February 2003). "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. PMC 6468321 . PMID 12620232.
↑ Helenius J, Brouhard G, Kalaidzidis Y, Diez S, Howard J (May 2006). "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. PMID 16672973. S2CID 4408328.
↑ Moriwaki T, Goshima G (November 2016). "Five factors can reconstitute all three phases of microtubule polymerization dynamics". The Journal of Cell Biology. 215 (3): 357–368. doi:10.1083/jcb.201604118. PMC 5100292 . PMID 27799364.

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[MCB_Mitosis-1] 1 2 3 4 Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (January 2002). "Mitosis". Molecular Biology of the Cell (4th ed.). New York: Garland Science. ISBN 978-0-7167-3706-3.

[2] Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J (January 2000). "Microtubule Structures". Molecular Cell Biology (4th ed.). ISBN 978-0-7167-4366-8.

[3] Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (January 2002). "The Self-Assembly and Dynamic Structure of Cytoskeletal Filaments". Molecular Biology of the Cell (4th ed.). New York: Garland Science. ISBN 978-0-7167-3706-3.

[4] Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J (January 2000). "Microtubule Dynamics and Associated Proteins". Molecular Biology of the Cell (4th ed.). New York: Garland Science. ISBN 978-0-7167-3706-3.

[Bowne-Anderso_2015-5] 1 2 3 4 Bowne-Anderson H, Hibbel A, Howard J (December 2015). "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. PMC 4783267 . PMID 26616192.

[6] Marklund U, Larsson N, Gradin HM, Brattsand G, Gullberg M (October 1996). "Oncoprotein 18 is a phosphorylation-responsive regulator of microtubule dynamics". The EMBO Journal. 15 (19): 5290–5298. doi:10.1002/j.1460-2075.1996.tb00914.x. PMC 452273 . PMID 8895574.

[:0-7] 1 2 Brattsand G (August 2000). "Correlation of oncoprotein 18/stathmin expression in human breast cancer with established prognostic factors". British Journal of Cancer. 83 (3): 311–318. doi:10.1054/bjoc.2000.1264. PMC 2374559 . PMID 10917544.

[8] Larsson N, Marklund U, Gradin HM, Brattsand G, Gullberg M (September 1997). "Control of microtubule dynamics by oncoprotein 18: dissection of the regulatory role of multisite phosphorylation during mitosis". Molecular and Cellular Biology. 17 (9): 5530–5539. doi:10.1128/MCB.17.9.5530. PMC 232401 . PMID 9271428.

[Hunter_2003-9] Hunter AW, Caplow M, Coy DL, Hancock WO, Diez S, Wordeman L, Howard J (February 2003). "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. PMC 6468321 . PMID 12620232.

[10] Helenius J, Brouhard G, Kalaidzidis Y, Diez S, Howard J (May 2006). "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. PMID 16672973. S2CID 4408328.

[11] Moriwaki T, Goshima G (November 2016). "Five factors can reconstitute all three phases of microtubule polymerization dynamics". The Journal of Cell Biology. 215 (3): 357–368. doi:10.1083/jcb.201604118. PMC 5100292 . PMID 27799364.

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