XMAP215-Dis1 family

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The XMAP215/Dis1 family is a highly conserved group of microtubule-associated proteins (MAPs) in eukaryotic organisms. [1] 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). [2]

Contents

Structure

The basic structure of the protein family consists of TOG (Tumor Overexpressed Gene) domains, ranging from 2-5 units. The family is categorized into three groups based on the number of TOG domains that specific protein contains. Higher eukaryotic organisms, categorized in the first group, contain five, N-terminus TOG domains and a variable region that connects to a C-terminal domain. [3] These domains are highly conserved monomeric sequences. The second group consists of only the Caenorhabditis elegans protein zyg-9, which has three TOG domains. [3] It is similar, though, to higher eukaryotes because of its variable region and C-terminal domain. The third group consists of lower eukaryotic organisms, mainly yeast, that contain only two TOG domains and a coiled-coil domain. [3]

The TOG3 domain in C. elegans zyg-9 Zyg-9 TOG3 domain.jpg
The TOG3 domain in C. elegans zyg-9

Thorough analysis of the TOG3 domain in zyg-9 provides a basic understanding of this domain that is conserved throughout all members of the XMAP215/Dis1 family. [3] Each domain consists of six HEAT (Huntingtin, Elongation factor 3, the PR65/A subunit of protein phosphatase 2A and the lipid kinase Tor) repeat units that are adjacently aligned. Each HEAT molecule consists of two α helices that are connected by a single loop. [3] These α helices form the wide, flat surface of the domain. The loops between HEAT repeats and between individual α helices run along the short side of the domain. This short region is necessary for binding to tubulin. An additional HEAT repeat, localized between the first and second HEAT repeat, is exclusive to the TOG3 domain in zyg-9 and the TOG5 domains in the first group family proteins. [3]

The C-terminal end of the protein has group-specific characteristics. In the third protein group, the coiled-coil domain is essential for dimerization in simple eukaryotes. [3] This is because simple eukaryotes such as yeast produce proteins in dimers. In first and second groups, the C-terminal domain is known to interact with transforming acidic coiled-coil protein 3 (TACC3), which transports the protein to the centrosomes during mitosis. [4]

Function

Mechanism model

XMAP215/Dis1 proteins can add or remove tubulin dimers in a two-step process. XMAP215 has been shown to bind to tubulin in a 1:1 complex, meaning that XMAP215 might not bind multiple tubulin dimers at once. [5] The αβ-tubulin dimer is known to interact with at least TOG domain, TOG1, which tightly binds inside the bend of the tubulin dimer and is also found beyond the direct plus-end of the microtubule. [6] The tubulin then “straightens,” which forms a weak interaction with TOG1. TOG2, however, can form a tight bind to straight tubulin. Much like a hand-off, TOG1 releases the dimer, which then binds to TOG2. TOG2 then integrates the tubulin dimer into the lattice, extending the microtubule. [6]

Microtubule function

Microtubule lattice with ab-tubulin dimers Microtubules.png
Microtubule lattice with αβ-tubulin dimers

XMAP215/Dis1 family proteins promote both growth and reduction of microtubule length, depending on the concentration of free tubulin; this is known as dynamic instability. [1] Protein behavior is also cell-cycle dependent. Reducing ch-TOG expression leads to improper alignment of the chromosomes during metaphase. [7] One study suggests that in Schizosaccharomyces pombe , the protein Cdc2 regulates Dis1 through phosphorylation and dephosphorylation during metaphase and anaphase. Phosphorylating Dis1 leads to localization at the kinetochores during metaphase, whereas dephosphorylation during anaphase leads to an accumulation of Dis1 on microtubule spindles. [8] In Drosophila, the family member Mini spindles (Msps) is essential for maintaining the integrity of mitotic spindles, which are important for separating chromosomes during mitosis. Reducing Msps activity creates short microtubules, which describes the name of the gene. [9] Msps is also important during oogenesis. When oocytes are depleted of Msps expression, bicoid mRNA localization is less efficient during early stages of oogenesis, but then completely dispersed later in development. [10] Msps is not only responsible for transporting bicoid mRNA throughout the cell, but it also localizes mRNA to the anterior (head) end of the oocyte [10] Additionally, this gene is critical for the organization of tubular endoplasmic reticulum and in Exuperantia protein localization. Exuperantia is necessary for accumulating bicoid mRNA in the head region of the oocyte. [11] Another key function of XMAP215 in microtubule dynamics is in the regulation of axon guidance. [12] This is when microtubules extend into or retract from the axonal growth cone, which guides movement by receiving concentrated signaling cues. [13] In Drosophila, Msps promotes microtubule dynamics in axonal guidance at the embryonic ventral nerve cord midline. [14]


Interactions with plus-end tracking proteins (+TIPs)

Plus-end tracking proteins are enzymes that localize and interact at the plus-end of microtubules. When tagged with green fluorescent protein (GFP), +TIPs can be visualized and tracked in the direction of microtubule growth. As a +TIP, XMAP215/Dis1 family proteins interact with other +TIPs. [2]

EB1

In Xenopus , XMAP215 and EB1 have been reported to interact with each other. While XMAP215 functions to both grow and shrink the microtubule, EB1 is only present during growth. [15] Alone, these proteins have mild effects on microtubule growth. Together, these proteins act in synergy and lengthen microtubules at a much greater rate. Without XMAP215, EB1 does not have a tubulin polymerase that can efficiently construct the microtubule plus-end with free tubulin. Without EB1, XMAP215 continues to add tubulin to the plus-end, but the integrity of the microtubule lattice becomes compromised. This is because EB1 binds to the microtubule lattice as a stabilizer to keep the tubulin straight. [15]

Members

Group 1 (5 TOG domains)

XMAP215: Xenopus Microtubule-associated protein, found in Xenopus species. The number 215 refers to the size of the protein, which is 215 kDa. This protein was discovered in 1987 through the investigation of microtubule regulation in Xenopus oocytes. [16] In 2008, the protein was identified as a plus-end microtubule polymerase. [5]

ch-Tog: colonic and hepatic Tumour Overexpressing Gene, found in Homo sapiens . It was first identified in humans in 1996 as an overexpressed gene in tumors, but was recognized for its plus-end microtubule regulation in 1998. [17]

Msps: Mini spindles. This protein is found in Drosophila species. This protein was discovered in 1999. [9]

DdCP224: Dictyostelium discoideum Centrosomal Protein. This protein's size is approximately 224 kDa. It was detected in 2000 through immunoscreening of DNA libraries for centrosomal proteins. [18]

Mor1: microtubule organisation gene 1. Found in Arabidopsis thaliana . This protein was discovered in 2001 as an organizer of cortical microtubules [19]

Group 2 (3 TOG domains)

zyg-9: zygotic defective mutant, found in C. elegans. In 1976, this gene was identified when zygotes, with such a mutation, failed to hatch. Zyg-9 was identified as a microtubule regulator in 1980. [20]

Group 3 (2 TOG domains)

alp14/Dis1: altered polarity/Defect in sister chromatid disjoining. These proteins are found in S. pombe. Dis1 is the preferred homologue in colder temperatures, while alp14 is preferred in higher temperatures. Dis1 was recognized in 1988, whereas its homologue alp14 was identified in 2001 [20]

Stu2p: suppressors of a tubulin mutation. This protein is found in Saccharomyces cerevisiae . It was discovered in 1997 through a screen and was found to influence microtubule regulation. [21] AlpA: alkaline phosphotase, found in Aspergillus nidulans . In 2007, this protein was identified to interact with microtubule plus ends and also localize at spindle bodies, which is characteristic of XMAP215/Dis1 family proteins. [22]

Related Research Articles

<span class="mw-page-title-main">Microtubule</span> Polymer of tubulin that forms part of the cytoskeleton

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 is 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.

<span class="mw-page-title-main">Tubulin</span> Superfamily of proteins that make up microtubules

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.

<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.

<span class="mw-page-title-main">Stathmin</span> Protein in Eukaryotes

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

<span class="mw-page-title-main">Aurora kinase A</span> Protein-coding gene in the species Homo sapiens

Aurora kinase A also known as serine/threonine-protein kinase 6 is an enzyme that in humans is encoded by the AURKA gene.

In cell biology, microtubule nucleation is the event that initiates de novo formation of microtubules (MTs). These filaments of the cytoskeleton typically form through polymerization of α- and β-tubulin dimers, the basic building blocks of the microtubule, which initially interact to nucleate a seed from which the filament elongates.

<span class="mw-page-title-main">Aurora kinase B</span> Protein

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

<span class="mw-page-title-main">Dynactin</span>

Dynactin is a 23 subunit protein complex that acts as a co-factor for the microtubule motor cytoplasmic dynein-1. It is built around a short filament of actin related protein-1 (Arp1).

<span class="mw-page-title-main">MAPRE1</span> Protein-coding gene in the species Homo sapiens

Microtubule-associated protein RP/EB family member 1 is a protein that in humans is encoded by the MAPRE1 gene.

<span class="mw-page-title-main">MAPRE2</span> Protein-coding gene in the species Homo sapiens

Microtubule-associated protein RP/EB family member 2 is a protein that in humans is encoded by the MAPRE2 gene.

<span class="mw-page-title-main">TPX2</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">PCNT</span> Protein-coding gene in the species Homo sapiens

Pericentrin (kendrin), also known as PCNT and pericentrin-B (PCNTB), is a protein which in humans is encoded by the PCNT gene on chromosome 21. This protein localizes to the centrosome and recruits proteins to the pericentriolar matrix (PCM) to ensure proper centrosome and mitotic spindle formation, and thus, uninterrupted cell cycle progression. This gene is implicated in many diseases and disorders, including congenital disorders such as microcephalic osteodysplastic primordial dwarfism type II (MOPDII) and Seckel syndrome.

<span class="mw-page-title-main">ANLN</span> Mammalian protein found in Homo sapiens

Anillin is a conserved protein implicated in cytoskeletal dynamics during cellularization and cytokinesis. The ANLN gene in humans and the scraps gene in Drosophila encode Anillin. In 1989, anillin was first isolated in embryos of Drosophila melanogaster. It was identified as an F-actin binding protein. Six years later, the anillin gene was cloned from cDNA originating from a Drosophila ovary. Staining with anti-anillin antibody showed the anillin localizes to the nucleus during interphase and to the contractile ring during cytokinesis. These observations agree with further research that found anillin in high concentrations near the cleavage furrow coinciding with RhoA, a key regulator of contractile ring formation.

<span class="mw-page-title-main">CKAP5</span> Protein-coding gene in the species Homo sapiens

Cytoskeleton-associated protein 5 is a microtubule-associated protein that in humans is encoded by the CKAP5 gene. It is the homolog of the Xenopus protein XMAP215 and is also known as ch-Tog.

Catastrophin 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.

<span class="mw-page-title-main">HEAT repeat</span> Protein tandem repeat

A HEAT repeat is a protein tandem repeat structural motif composed of two alpha helices linked by a short loop. HEAT repeats can form alpha solenoids, a type of solenoid protein domain found in a number of cytoplasmic proteins. The name "HEAT" is an acronym for four proteins in which this repeat structure is found: Huntingtin, elongation factor 3 (EF3), protein phosphatase 2A (PP2A), and the yeast kinase TOR1. HEAT repeats form extended superhelical structures which are often involved in intracellular transport; they are structurally related to armadillo repeats. The nuclear transport protein importin beta contains 19 HEAT repeats.

<span class="mw-page-title-main">MDia1</span> Protein

mDia1 is a member of the protein family called the formins and is a Rho effector. It is the mouse version of the diaphanous homolog 1 of Drosophila. mDia1 localizes to cells' mitotic spindle and midbody, plays a role in stress fiber and filopodia formation, phagocytosis, activation of serum response factor, formation of adherens junctions, and it can act as a transcription factor. mDia1 accelerates actin nucleation and elongation by interacting with barbed ends of actin filaments. The gene encoding mDia1 is located on Chromosome 18 of Mus musculus and named Diap1.

Centralspindlin is a motor complex implicated in cell division. It contributes to virtually every step in cytokinesis, It is highly conserved in animal cells as a component of the spindle midzone and midbody. Centralspindlin is required for the assembly of the mitotic spindle as well as for microtubule bundling and anchoring of midbody microtubules to the plasma membrane. This complex is also implicated in tethering the spindle apparatus to the plasma membrane during cytokinesis This interaction permits cleavage furrow ingression. In addition, centralspindlin's interaction with the ESCRT III allows for abscission to occur.

<span class="mw-page-title-main">Microtubule plus-end tracking protein</span>

Microtubule plus-end/positive-end tracking proteins or +TIPs are a type of microtubule associated protein (MAP) which accumulate at the plus ends of microtubules. +TIPs are arranged in diverse groups which are classified based on their structural components; however, all classifications are distinguished by their specific accumulation at the plus end of microtubules and their ability to maintain interactions between themselves and other +TIPs regardless of type. +TIPs can be either membrane bound or cytoplasmic, depending on the type of +TIPs. Most +TIPs track the ends of extending microtubules in a non-autonomous manner.

References

  1. 1 2 Kinoshita, Kazuhisa; Bianca Habermann and Anthony Hyman (June 2002). "XMAP215: a key component of the dynamic microtubule cytoskeleton". Trends in Cell Biology. 12 (6): 267–273. doi:10.1016/S0962-8924(02)02295-X. PMID   12074886.
  2. 1 2 Galjart, Niels (June 2010). "Plus-End-Tracking Proteins and Their Interactions at Microtubule Ends". Current Biology. 20 (12): R528–37. doi: 10.1016/j.cub.2010.05.022 . PMID   20620909. S2CID   17558620.
  3. 1 2 3 4 5 6 7 Al-Bassam, Jawdat; Nicholas Larsen; Anthony Hyman; Stephen Harrison (March 2007). "Crystal Structure of a TOG Domain: Conserved Features of XMAP215/Dis1-Family TOG Domains and Implications for Tubulin Binding". Structure. 15 (3): 355–362. doi: 10.1016/j.str.2007.01.012 . PMID   17355870.
  4. ↑ Kinoshita, Kazuhisa; Tim L. Noetzel; Laurence Pelletier; Karl Mechtler; David N. Drechsel; Anne Schwager; Mike Lee; Jordan W. Raff; Anthony A. Hyman (September 19, 2005). "Aurora A phosphorylation of TACC3/maskin is required for centrosome-dependent microtubule assembly in mitosis". Journal of Cell Biology. 170 (7): 1047–1055. doi:10.1083/jcb.200503023. PMC   2171544 . PMID   16172205.
  5. 1 2 Brouhard, Gary; Jeffrey Stear; Tim Noetzel; Jawdat Al-Bassam; Kazuhisa Kinoshita; Stephen Harrison; Jonathon Howard; Anthony Hyman (January 11, 2008). "XMAP215 is a processive microtubule polymerase". Cell. 132 (1): 79–88. doi:10.1016/j.cell.2007.11.043. PMC   2311386 . PMID   18191222.
  6. 1 2 Ayaz, Pelin; Xuecheng Ye; Patrick Huddleston; Chad Brautigam; Luke Rice (August 2012). "A TOG:ab-tubulin Complex Structure Reveals Conformation-Based Mechanisms for a Microtubule Polymerase". Science. 337 (6096): 857–60. Bibcode:2012Sci...337..857A. doi:10.1126/science.1221698. PMC   3734851 . PMID   22904013.
  7. ↑ Gergely, Fanni; Viji Daviam; Jordan Raff (2003). "The ch-TOG/XMAP215 protein is essential for spindle pole organization in human somatic cells". Genes & Development. 17 (3): 336–41. doi:10.1101/gad.245603. PMC   195983 . PMID   12569123.
  8. ↑ Keita, Aoki; Yukinobu Nakaseko; Kazuhisa Kinoshita; Gohta Goshima; Mitsuhiro Yanagida (August 2006). "Cdc2 Phosphorylation of the Fission Yeast Dis1 Ensures Accurate Chromosome Segregation". Current Biology. 16 (16): 1627–1635. doi: 10.1016/j.cub.2006.06.065 . PMID   16920624.
  9. 1 2 Cullen, C. Fiona; Peter Deák; David Glover; Hiroyuki Ohkura (September 1999). "A Gene Encoding a Conserved Microtubule-Associated Protein Required for the Integrity of the Mitotic Spindle in Drosophila" (PDF). Journal of Cell Biology. 146 (5): 1005–1018. doi:10.1083/jcb.146.5.1005. PMC   2169485 . PMID   10477755.
  10. 1 2 Moon, Woongjoon; Tulle Hazelrigg (November 2004). "The Drosophila Microtubule-Associated Protein Mini Spindles Is Required for Cytoplasmic Microtubules in Oogenesis". Current Biology. 14 (21): 1957–1961. doi: 10.1016/j.cub.2004.10.023 . PMID   15530399.
  11. ↑ Pokrywka, Nancy; Anna Payne-Tobin; Kathleen Raley-Susman; Sasha Swartzman (May 2009). "Microtubules, the ER and Exu: New associations revealed by analysis of mini spindles mutations". Mechanisms of Development. 126 (5–6): 289–300. doi:10.1016/j.mod.2009.03.002. PMC   2731561 . PMID   19303437.
  12. ↑ Lowery, Laura Anne; Alina Stout; Anna E Faris; Liya Ding; Michelle A Baird; Michael Davidson; Gaudenz Danuse; David Van Vector (December 2013). "Growth cone-specific functions of XMAP215 in restricting microtubule dynamics and promoting axonal outgrowth" (PDF). Neural Development. 8: 22. doi: 10.1186/1749-8104-8-22 . PMC   3907036 . PMID   24289819.
  13. ↑ Lowery, Laura Anne; David Van Vector (May 2009). "The trip of the tip: understanding the growth cone machinery". Nature Reviews Molecular Cell Biology. 10 (5): 332–43. doi:10.1038/nrm2679. PMC   2714171 . PMID   19373241.
  14. ↑ Lowery, L. A.; Lee, H.; Lu, C.; Murphy, R.; Obar, R. A.; Zhai, B.; Schedl, M.; Van Vactor, D.; Zhan, Y. (2010). "Parallel Genetic and Proteomic Screens Identify Msps as a CLASP-Abl Pathway Interactor in Drosophila". Genetics. 185 (4): 1311–1325. doi:10.1534/genetics.110.115626. ISSN   0016-6731. PMC   2927758 . PMID   20498300.
  15. 1 2 Zanic, Marija; Per Widlund; Anthony Hyman; Jonathon Howard (June 2013). "Synergy between XMAP215 and EB1 increases microtubule growth rates to physiological levels". Nature Cell Biology. 15 (6): 688–93. doi:10.1038/ncb2744. PMID   23666085. S2CID   3025200.
  16. ↑ Gard, David; Marc Kirschner (November 1987). "A Microtubule-associated Protein from Xenopus Eggs That Specifically Promotes Assembly at the Plus-End". The Journal of Cell Biology. 105 (5): 2203–2215. doi: 10.1083/jcb.105.5.2203 . PMC   2114854 . PMID   2890645.
  17. ↑ Charrasse, Sophie; Marianne Schroeder; Cécile Gauthier-Rouviere; Fabrice Ango; Lynne Cassimeris; David. L. Gard; Christian Larroque (April 1998). "The TOGp protein is a new human microtubule-associated protein homologous to the Xenopus XMAP215". Journal of Cell Science. 111 ( Pt 10) (10): 1371–83. doi:10.1242/jcs.111.10.1371. PMID   9570755.
  18. ↑ Graf, Ralph; Christine Daunderer; Manfred Schliwa (April 2000). "Dictyostelium DdCP224 is a microtubule-associated protein and a permanent centrosomal resident involved in centrosome duplication". Journal of Cell Science. 113 ( Pt 10) (10): 1747–58. doi: 10.1242/jcs.113.10.1747 . PMID   10769206.
  19. ↑ Whittington, Angela; Oliver Vugrek; Ke Jun Wei; Nortrud G. Hasenbein; Keiko Sugimoto; Madeleine C. Rashbrooke; Geoffrey O. Wasteneys (April 2001). "MOR1 is essential for organizing cortical microtubules in plants". Nature. 411 (6837): 610–613. Bibcode:2001Natur.411..610W. doi:10.1038/35079128. PMID   11385579. S2CID   205017664.
  20. 1 2 Matthews, Lisa; Philip Carter; Danielle Thierry-Mieg; Ken Kemphues (June 1998). "ZYG-9, A Caenorhabditis elegans Protein Required for Microtubule Organization and Function, Is a Component of Meiotic and Mitotic Spindle Poles". Journal of Cell Biology. 141 (5): 1159–1168. doi:10.1083/jcb.141.5.1159. PMC   2137183 . PMID   9606208.
  21. ↑ Nakaseko, Yukinobu Jeremy; Gohta Goshima; Jun Morishita; Mitsuhiro Yanagida (November 2000). "M phase–specific kinetochore proteins in fission yeast". Current Biology. 11 (8): 537–549. doi: 10.1016/S0960-9822(01)00155-5 . PMID   11369198. S2CID   18195930.
  22. ↑ Enke, C.; Zekert, N.; Veith, D.; Schaaf, C.; Konzack, S.; Fischer, R. (March 2007). "Aspergillus nidulans Dis1/XMAP215 Protein AlpA Localizes to Spindle Pole Bodies and Microtubule Plus Ends and Contributes to Growth Directionality". Eukaryotic Cell. 6 (3): 555–562. doi:10.1128/EC.00266-06. PMC   1828926 . PMID   17237365.
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