Wikipedia

ANLN

(Redirected from Anillin)
Not to be confused with Aniline.
"Anillin" redirects here. For similar words, see Aniline (disambiguation).

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.[5] In 1989, anillin was first isolated in embryos of Drosophila melanogaster. It was identified as an F-actin binding protein.[6] Six years later, the anillin gene was cloned from cDNA originating from a Drosophila ovary. Staining with anti-anillin (Antigen 8) antibody showed the anillin localizes to the nucleus during interphase and to the contractile ring during cytokinesis.[7] 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.[8]

ANLN
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesANLN, Scraps, scra, FSGS8, anillin actin binding protein, anillin, actin binding protein
External IDsOMIM: 616027 MGI: 1920174 HomoloGene: 41281 GeneCards: ANLN
Orthologs
SpeciesHumanMouse
Entrez

54443

68743

Ensembl

ENSG00000011426

ENSMUSG00000036777

UniProt

Q9NQW6

Q8K298

RefSeq (mRNA)

NM_001284301
NM_001284302
NM_018685

NM_028390

RefSeq (protein)

NP_001271230
NP_001271231
NP_061155

NP_082666
NP_001391862

Location (UCSC)Chr 7: 36.39 – 36.45 MbChr 9: 22.24 – 22.3 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

The name of the protein anillin originates from a Spanish word, anillo. Anillo means ring and shows that the name anillin references the observed enrichment of anillins at the contractile ring during cytokinesis. Anillins are also enriched at other actomyosin rings, most significantly, those at the leading edge of the Drosophila embryo during cellularization. These actomyosin rings invaginate to separate all nuclei for one another in the syncytial blastoderm.[5]

Structure edit

Anillin has a unique multi-domain structure. At the N-terminus, there is an actin- and myosin-binding domain. At the C-terminus, there is a PH domain. The PH domain is conserved and essential for anillin functionality.[8] The human anillin cDNA, located on Chr7, encodes a 1,125–amino acid protein with a predicted molecular mass of 124 kD and a pI of 8.1. The mouse anillin gene is located on Chromosome 9.[9]

There are also numerous anillin-like protein homologues found outside of metazoans. In Schizosaccharomyces pombe (fission yeast), there are Mid1p and Mid2p. These two anillin-like proteins do not have any overlap in their functions. Mid1p has been characterized as a key regulator in cytokinesis, responsible for arranging contractile ring assembly and positioning.[10] Mid2p acts later in cytokinesis to organize septins during septation, or the invagination of inner membranes, outer membranes, and the cell wall that occurs in order to separate daughter cells completely.[11] Saccharomyces cerevisiae (budding yeast) also have two anillin-like proteins, Boi1p and Boi2p. Boi1p and Boi2p localize to the nucleus and contractile ring at the bud neck, respectively. They are essential for cell growth and bud formation.[12]

 
The domains found in anillin across species

Function edit

Anillins are required for the faithfulness of cytokinesis and its F-actin-, myosin-, and septin-binding domains implicate anillin in actomyosin cytoskeletal organization. In agreement with this belief, anillin-mutant cells have disrupted contractile rings. Additionally, it is hypothesized that anillin couples the actomyosin cytoskeleton to microtubules by binding MgcRacGAP/CYK-4/RacGAP50C.[13]

Anillins have also been shown to organize the actomyosin cytoskeleton into syncytial structures observed in Drosophila embryos or C. elegans gonads. ANI-1 and ANI-2 (proteins homologous to anillin) are essential for embryonic viability in both organisms. ANI-1 is required for cortical ruffling, pseudocleavage, and all contractile events that occur in embryos prior to mitosis. ANI-1 is also crucial for segregation of polar bodies during meiosis. ANI-2 functions in the maintenance of the structure of the central core of the cytoplasm, the rachis, during oogenesis. ANI-2 ensures oocytes do not disconnect prematurely from the rachis, thereby leading to the generation of embryos of varying sizes.[14]

In vitro experiments suggest that anillin drives myosin-independent actin contractility.[15]

Binding Partners edit

Actin edit

Anillin specifically binds F-actin, rather than G-actin. Binding of F-actin by anillin only occurs during cell division. Anillin also bundles actin filaments together and drives their relative sliding.[15] This contractile behavior is independent of myosin and ATP and may couple with actin filament disassembly. Amino acids 258-340 are sufficient and necessary for F-actin binding in Drosophila, but amino acids 246-371 are necessary to bundle actin filaments.[7] The ability of anillin to bind to and bundle actin together is conversed through many species. It is hypothesized that by regulating actin bundling, anillin increases the efficiency of actomyosin contractility during cell division. Both anillin and F-actin are found in contractile structures. They are recruited independently to the contractile ring, but F-actin increases the efficiency of anillin targeting.[5] Anillin may also be involved in promoting the polymerization of F-actin by stabilizing formin mDia2 in an active form.[16]

Myosin edit

Anillin interacts directly with non-muscle myosin II and interacts indirectly with myosin via F-actin. Residues 142-254 (near the N-terminus) are essential for anillin binding myosin in Xenopus. The interaction of anillin and myosin is also dependent on phosphorylation of the myosin light chain.[17] The interaction of myosin and anillin does not seem to serve in recruitment, but rather organization of myosin. In Drosophila, anillin is necessary to organize myosin into rings in the cellularization front.[18] Depletion of anillin in Drosophila and humans leads to changes in the spatial and temporal stability of myosin during cytokinesis.[19] In C. elegans, ANI-1 organizes myosin into foci during cytokinesis and establishment of polarity, whereas, ANI-2 is a requirement for the maintenance of myosin-rich contractile lining of oogenic gonads.[14]

Septins edit

Septin localization during cytokinesis and cellularization is dependent on its association with anillin.[20] The direct interaction between anillin and septins was first shown by the interaction seen between Xenopus anillin and a minimal reconstituted heterooligomer of human septins 2, 6, and 7.[21] The ability of anillin to bind to septins is dependent on the C-terminal domain, which contains a terminal PH domain and an upstream sequence known as the “Anillin Homology” (AH) domain.[9]

Rho edit

The AH domain of human anillin is essential for its interaction with RhoA. Depletion of RhoA halts contractile ring assembly and ingression, whereas, anillin depletion leads to a less severe phenotype when the contractile ring forms and ingresses partially. Depletion of anillin in Drosophila spermatocytes greatly reduces the localization of Rho and F-actin to equatorial regions.[19]

Ect2 edit

Anillin interacts with Ect2, further supporting the idea that anillin stabilizes RhoA localization since Ect2 is an activator of RhoA. Independent of RhoA, the interaction between anillin and Ect2 occurs. This interaction is essential of the GEF activity of Ect2 and requires the AH domain of anillin and the PH domain of Ect2.[22]

Cyk-4 edit

Drosophila anillin interacts with Cyk-4, a central spindle protein, indicating that anillin may have a role in determining the division plane during cytokinesis.[23] In anillin-depleted larval cells, the central spindle does not extend to the cortex.[24] Human anillin-depleted cells show improperly positioned and distorted central spindles.[25]

Microtubules edit

Anillin was first isolated from Drosophila by harnessing its interactions with both F-actin and microtubules.[26] Furthermore, anillin-rich structures that form after Latrunculin A treatment of Drosophila cells localize to the plus-ends of microtubules.[27] The interaction between anillin and microtubules suggest that anillin may serve as a signaling factor to relay the position of the mitotic spindle to the cortex to ensure appropriate contractile ring formation during cytokinesis.[5]

Regulation edit

Anillins in metazoans are heavily phosphorylated; however, the kinases responsible for the phosphorylation are unknown at the present time. In humans and Drosophila, anillins are recruited to the equatorial cortex in a RhoA-dependent manner. This recruitment is independent of other cytoskeletal Rho targets such as myosin, F-actin, and Rho-kinase. It has been observed that anillin proteolysis is triggered after mitotic exit by the Anaphase Promoting Complex (APC).

Most anillins can be sequestered to the nucleus during interphase, but there are exceptions – Drosophila anilins in the early embryo, C. elegans ANI-1 in early embryos, C. elegans ANI-2 in oogenic gonads, and Mid2p in fission yeast. These anillins that are not sequestered during interphase suggest that anillins may also regulate cytoskeletal dynamics outside the contractile ring during cytokinesis.[6]

Role in Diseases edit

Anillin is critical for cell division and therefore development and homeostasis in metazoans. In recent years, the expression levels of anillin have been shown to correlate to the metastatic potential of human tumours. In colorectal cancer, expression levels of anillin are higher in tumours and when anillin was over-expressed in HT29 cells, a classical colorectal cancer cell line, the cells showed faster replication kinetics due to the lengthening of G2/M phase. Increasing the expression of anillin also led to further invasiveness and migration of numerous colorectal cancer cell lines. The hypothesis from such observations is that anillin promotes EMT and cell migration through cytoskeletal remodeling, leading to enhanced proliferation, invasion, and mobility of tumour cells.[28][29]

References edit

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000011426 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000036777 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b c d Piekny AJ, Maddox AS (December 2010). "The myriad roles of Anillin during cytokinesis" (PDF). Seminars in Cell & Developmental Biology. 21 (9): 881–91. doi:10.1016/j.semcdb.2010.08.002. PMID 20732437.
  6. ^ a b Zhang L, Maddox AS (February 2010). "Anillin". Current Biology. 20 (4): R135-6. Bibcode:2010CBio...20.R135Z. doi:10.1016/j.cub.2009.12.017. PMID 20178751.
  7. ^ a b Field CM, Alberts BM (October 1995). "Anillin, a contractile ring protein that cycles from the nucleus to the cell cortex". The Journal of Cell Biology. 131 (1): 165–78. doi:10.1083/jcb.131.1.165. PMC 2120607. PMID 7559773.
  8. ^ a b Piekny AJ, Glotzer M (January 2008). "Anillin is a scaffold protein that links RhoA, actin, and myosin during cytokinesis". Current Biology. 18 (1): 30–6. Bibcode:2008CBio...18...30P. doi:10.1016/j.cub.2007.11.068. PMID 18158243. S2CID 6310134.
  9. ^ a b Oegema K, Savoian MS, Mitchison TJ, Field CM (August 2000). "Functional analysis of a human homologue of the Drosophila actin binding protein anillin suggests a role in cytokinesis". The Journal of Cell Biology. 150 (3): 539–52. doi:10.1083/jcb.150.3.539. PMC 2175195. PMID 10931866.
  10. ^ Saha S, Pollard TD (October 2012). "Characterization of structural and functional domains of the anillin-related protein Mid1p that contribute to cytokinesis in fission yeast". Molecular Biology of the Cell. 23 (20): 3993–4007. doi:10.1091/mbc.E12-07-0536. PMC 3469515. PMID 22918954.
  11. ^ Tasto JJ, Morrell JL, Gould KL (March 2003). "An anillin homologue, Mid2p, acts during fission yeast cytokinesis to organize the septin ring and promote cell separation". The Journal of Cell Biology. 160 (7): 1093–103. doi:10.1083/jcb.200211126. PMC 2172762. PMID 12668659.
  12. ^ Toya M, Iino Y, Yamamoto M (August 1999). "Fission yeast Pob1p, which is homologous to budding yeast Boi proteins and exhibits subcellular localization close to actin patches, is essential for cell elongation and separation". Molecular Biology of the Cell. 10 (8): 2745–57. doi:10.1091/mbc.10.8.2745. PMC 25510. PMID 10436025.
  13. ^ D'Avino PP, Takeda T, Capalbo L, Zhang W, Lilley KS, Laue ED, et al. (April 2008). "Interaction between Anillin and RacGAP50C connects the actomyosin contractile ring with spindle microtubules at the cell division site". Journal of Cell Science. 121 (Pt 8): 1151–8. doi:10.1242/jcs.026716. PMID 18349071.
  14. ^ a b Maddox AS, Habermann B, Desai A, Oegema K (June 2005). "Distinct roles for two C. elegans anillins in the gonad and early embryo". Development. 132 (12): 2837–48. doi:10.1242/dev.01828. PMID 15930113.
  15. ^ a b Kučera O, Siahaan V, Janda D, Dijkstra SH, Pilátová E, Zatecka E, et al. (2021). "Anillin propels myosin-independent constriction of actin rings". Nature Communications. 12 (1): 4595. Bibcode:2021NatCo..12.4595K. doi:10.1038/s41467-021-24474-1. PMC 8319318. PMID 34321459.
  16. ^ Watanabe S, Okawa K, Miki T, Sakamoto S, Morinaga T, Segawa K, et al. (September 2010). "Rho and anillin-dependent control of mDia2 localization and function in cytokinesis". Molecular Biology of the Cell. 21 (18): 3193–204. doi:10.1091/mbc.E10-04-0324. PMC 2938385. PMID 20660154.
  17. ^ Straight AF, Field CM, Mitchison TJ (January 2005). "Anillin binds nonmuscle myosin II and regulates the contractile ring". Molecular Biology of the Cell. 16 (1): 193–201. doi:10.1091/mbc.E04-08-0758. PMC 539163. PMID 15496454.
  18. ^ Field CM, Coughlin M, Doberstein S, Marty T, Sullivan W (June 2005). "Characterization of anillin mutants reveals essential roles in septin localization and plasma membrane integrity". Development. 132 (12): 2849–60. doi:10.1242/dev.01843. PMID 15930114.
  19. ^ a b Goldbach P, Wong R, Beise N, Sarpal R, Trimble WS, Brill JA (May 2010). "Stabilization of the actomyosin ring enables spermatocyte cytokinesis in Drosophila". Molecular Biology of the Cell. 21 (9): 1482–93. doi:10.1091/mbc.E09-08-0714. PMC 2861608. PMID 20237160.
  20. ^ Versele M, Thorner J (August 2005). "Some assembly required: yeast septins provide the instruction manual". Trends in Cell Biology. 15 (8): 414–24. doi:10.1016/j.tcb.2005.06.007. PMC 1761124. PMID 16009555.
  21. ^ Kinoshita M, Field CM, Coughlin ML, Straight AF, Mitchison TJ (December 2002). "Self- and actin-templated assembly of Mammalian septins". Developmental Cell. 3 (6): 791–802. doi:10.1016/S1534-5807(02)00366-0. PMID 12479805.
  22. ^ Solski PA, Wilder RS, Rossman KL, Sondek J, Cox AD, Campbell SL, et al. (June 2004). "Requirement for C-terminal sequences in regulation of Ect2 guanine nucleotide exchange specificity and transformation". The Journal of Biological Chemistry. 279 (24): 25226–33. doi:10.1074/jbc.M313792200. PMID 15073184.
  23. ^ Glotzer M (January 2009). "The 3Ms of central spindle assembly: microtubules, motors and MAPs". Nature Reviews. Molecular Cell Biology. 10 (1): 9–20. doi:10.1038/nrm2609. PMC 2789570. PMID 19197328.
  24. ^ Gregory SL, Ebrahimi S, Milverton J, Jones WM, Bejsovec A, Saint R (January 2008). "Cell division requires a direct link between microtubule-bound RacGAP and Anillin in the contractile ring". Current Biology. 18 (1): 25–9. Bibcode:2008CBio...18...25G. doi:10.1016/j.cub.2007.11.050. PMID 18158242. S2CID 17517089.
  25. ^ Zhao WM, Fang G (September 2005). "Anillin is a substrate of anaphase-promoting complex/cyclosome (APC/C) that controls spatial contractility of myosin during late cytokinesis". The Journal of Biological Chemistry. 280 (39): 33516–24. doi:10.1074/jbc.M504657200. PMID 16040610.
  26. ^ Sisson JC, Field C, Ventura R, Royou A, Sullivan W (November 2000). "Lava lamp, a novel peripheral golgi protein, is required for Drosophila melanogaster cellularization". The Journal of Cell Biology. 151 (4): 905–18. doi:10.1083/jcb.151.4.905. PMC 2169433. PMID 11076973.
  27. ^ Hickson GR, O'Farrell PH (January 2008). "Rho-dependent control of anillin behavior during cytokinesis". The Journal of Cell Biology. 180 (2): 285–94. doi:10.1083/jcb.200709005. PMC 2213597. PMID 18209105.
  28. ^ Chuang HY, Ou YH (2014). Overexpression of anillin in colorectal cancer promoter the cell proliferation, cell mobility and cell invasion. Proceedings of the 105th Annual Meeting of the American Association for Cancer Research. San Diego, CA.
  29. ^ Wang G, Shen W, Cui L, Chen W, Hu X, Fu J (2016). "Overexpression of Anillin (ANLN) is correlated with colorectal cancer progression and poor prognosis". Cancer Biomarkers. 16 (3): 459–65. doi:10.3233/CBM-160585. PMID 27062703.

External links edit

Further reading edit

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