Home LiteratureArticle Details
PMID: 18267092 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Cell-type-specific TEV protease cleavage reveals cohesin functions in Drosophila neurons.

Developmental cell ·Vol. 14 ·No. 2 ·2008-02-00 ·Pages 239-51

Pauli A, Althoff F, Oliveira RA, Heidmann S, Schuldiner O, Lehner CF, Dickson BJ, Nasmyth K

Abstract

Cohesin is a highly conserved multisubunit complex that holds sister chromatids together in mitotic cells. At the metaphase to anaphase transition, proteolytic cleavage of the alpha kleisin subunit (Rad21) by separase causes cohesin's dissociation from chromosomes and triggers sister-chromatid disjunction. To investigate cohesin's function in postmitotic cells, where it is widely expressed, we have created fruit flies whose Rad21 can be cleaved by TEV protease. Cleavage causes precocious separation of sister chromatids and massive chromosome missegregation in proliferating cells, but not disaggregation of polytene chromosomes in salivary glands. Crucially, cleavage in postmitotic neurons is lethal. In mushroom-body neurons, it causes defects in axon pruning, whereas in cholinergic neurons it causes highly abnormal larval locomotion. These data demonstrate essential roles for cohesin in nondividing cells and also introduce a powerful tool by which to investigate protein function in metazoa.

MeSH Terms
Animals Axons/metabolism Cell Cycle Proteins/metabolism Choline/metabolism Chromatids/metabolism Chromosomal Proteins, Non-Histone/metabolism Chromosome Segregation Dendrites/metabolism Drosophila Proteins/metabolism Drosophila melanogaster/cytology,embryology,metabolism Embryo, Nonmammalian/cytology,metabolism Endopeptidases/metabolism Fertility Larva Locomotion Mitosis Mutation/genetics Neurons/cytology,metabolism Nuclear Proteins/metabolism Organ Specificity Protein Binding
Chemicals
Cell Cycle Proteins Chromosomal Proteins, Non-Histone Drosophila Proteins Nuclear Proteins cohesins vtd protein, Drosophila Endopeptidases TEV protease Choline
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Pauli Andrea
Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
Althoff Friederike
Oliveira Raquel A
Heidmann Stefan
Schuldiner Oren
Lehner Christian F
Dickson Barry J
Nasmyth Kim
References (47)
47 references, click to expand
  1. Condensin-dependent localisation of topoisomerase II to an axial chromosomal structure is required for sister chromatid resolution during mitosis.
    J Cell Sci. 2003 Dec 1;116(Pt 23):4763-76 PMID: 14600262
  2. Chromosome bi-orientation on the mitotic spindle.
    Philos Trans R Soc Lond B Biol Sci. 2005 Mar 29;360(1455):581-9 PMID: 15897181
  3. Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of cornelia de Lange syndrome with predominant mental retardation.
    Am J Hum Genet. 2007 Mar;80(3):485-94 PMID: 17273969
  4. NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome.
    Nat Genet. 2004 Jun;36(6):636-41 PMID: 15146185
  5. Polytene chromosomes: 70 years of genetic research.
    Int Rev Cytol. 2004;241:203-75 PMID: 15548421
  6. X-linked Cornelia de Lange syndrome owing to SMC1L1 mutations.
    Nat Genet. 2006 May;38(5):528-30 PMID: 16604071
  7. Axon pruning during Drosophila metamorphosis: evidence for local degeneration and requirement of the ubiquitin-proteasome system.
    Neuron. 2003 Jun 19;38(6):871-85 PMID: 12818174
  8. Depletion of Drad21/Scc1 in Drosophila cells leads to instability of the cohesin complex and disruption of mitotic progression.
    Curr Biol. 2003 Feb 4;13(3):208-18 PMID: 12573216
  9. Drosophila brakeless interacts with atrophin and is required for tailless-mediated transcriptional repression in early embryos.
    PLoS Biol. 2007 Jun;5(6):e145 PMID: 17503969
  10. Conditional modification of behavior in Drosophila by targeted expression of a temperature-sensitive shibire allele in defined neurons.
    J Neurobiol. 2001 May;47(2):81-92 PMID: 11291099
  11. Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis.
    Neuron. 1999 Mar;22(3):451-61 PMID: 10197526
  12. Two distinct pathways remove mammalian cohesin from chromosome arms in prophase and from centromeres in anaphase.
    Cell. 2000 Oct 27;103(3):399-410 PMID: 11081627
  13. The structure and function of SMC and kleisin complexes.
    Annu Rev Biochem. 2005;74:595-648 PMID: 15952899
  14. Cellular and axonal migrations are misguided along both body axes in the maternal-effect mau-2 mutants of Caenorhabditis elegans.
    Development. 1997 Dec;124(24):5115-26 PMID: 9362469
  15. A direct link between sister chromatid cohesion and chromosome condensation revealed through the analysis of MCD1 in S. cerevisiae.
    Cell. 1997 Oct 3;91(1):47-57 PMID: 9335334
  16. Association of cohesin and Nipped-B with transcriptionally active regions of the Drosophila melanogaster genome.
    Chromosoma. 2008 Feb;117(1):89-102 PMID: 17965872
  17. Cohesins: chromosomal proteins that prevent premature separation of sister chromatids.
    Cell. 1997 Oct 3;91(1):35-45 PMID: 9335333
  18. A screen for cohesion mutants uncovers Ssl3, the fission yeast counterpart of the cohesin loading factor Scc4.
    Curr Biol. 2006 May 9;16(9):875-81 PMID: 16682348
  19. CTCF is conserved from Drosophila to humans and confers enhancer blocking of the Fab-8 insulator.
    EMBO Rep. 2005 Feb;6(2):165-70 PMID: 15678159
  20. Different spindle checkpoint proteins monitor microtubule attachment and tension at kinetochores in Drosophila cells.
    J Cell Sci. 2004 Apr 1;117(Pt 9):1757-71 PMID: 15075237
  21. Drosophila cholinergic neurons and processes visualized with Gal4/UAS-GFP.
    Brain Res Gene Expr Patterns. 2001 Aug;1(1):73-82 PMID: 15018821
  22. Human Wapl is a cohesin-binding protein that promotes sister-chromatid resolution in mitotic prophase.
    Curr Biol. 2006 Dec 19;16(24):2406-17 PMID: 17112726
  23. Roles of the sister chromatid cohesion apparatus in gene expression, development, and human syndromes.
    Chromosoma. 2007 Feb;116(1):1-13 PMID: 16819604
  24. Development of the Drosophila mushroom bodies: sequential generation of three distinct types of neurons from a neuroblast.
    Development. 1999 Sep;126(18):4065-76 PMID: 10457015
  25. Effects of sister chromatid cohesion proteins on cut gene expression during wing development in Drosophila.
    Development. 2005 Nov;132(21):4743-53 PMID: 16207752
  26. Wapl controls the dynamic association of cohesin with chromatin.
    Cell. 2006 Dec 1;127(5):955-67 PMID: 17113138
  27. Nipped-B, a Drosophila homologue of chromosomal adherins, participates in activation by remote enhancers in the cut and Ultrabithorax genes.
    Genetics. 1999 Jun;152(2):577-93 PMID: 10353901
  28. Turning behavior in Drosophila larvae: a role for the small scribbler transcript.
    Genes Brain Behav. 2004 Oct;3(5):273-86 PMID: 15344921
  29. Cohesin-dependent regulation of Runx genes.
    Development. 2007 Jul;134(14):2639-49 PMID: 17567667
  30. At the heart of the chromosome: SMC proteins in action.
    Nat Rev Mol Cell Biol. 2006 May;7(5):311-22 PMID: 16633335
  31. The Drosophila meiotic kleisin C(2)M functions before the meiotic divisions.
    Chromosoma. 2004 Oct;113(4):177-87 PMID: 15375666
  32. Synergistic action of Drosophila cyclins A and B during the G2-M transition.
    EMBO J. 1993 Jan;12(1):65-74 PMID: 8428595
  33. Abnormal turning behavior in Drosophila larvae. Identification and molecular analysis of scribbler (sbb).
    Genetics. 2000 Jul;155(3):1161-74 PMID: 10880478
  34. Chromosomal cohesin forms a ring.
    Cell. 2003 Mar 21;112(6):765-77 PMID: 12654244
  35. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.
    Development. 1993 Jun;118(2):401-15 PMID: 8223268
  36. Functional links between Drosophila Nipped-B and cohesin in somatic and meiotic cells.
    Chromosoma. 2008 Feb;117(1):51-66 PMID: 17909832
  37. Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B.
    Nat Genet. 2004 Jun;36(6):631-5 PMID: 15146186
  38. Molecular architecture of SMC proteins and the yeast cohesin complex.
    Mol Cell. 2002 Apr;9(4):773-88 PMID: 11983169
  39. [Localization of cohesin complexes of polytene chromosomes of Drosophila melanogaster located on interbands].
    Genetika. 2003 Sep;39(9):1203-11 PMID: 14582389
  40. Precocious sister chromatid separation (PSCS) in Cornelia de Lange syndrome.
    Am J Med Genet A. 2005 Sep 15;138(1):27-31 PMID: 16100726
  41. Heat-inducible degron: a method for constructing temperature-sensitive mutants.
    Science. 1994 Mar 4;263(5151):1273-6 PMID: 8122109
  42. Localization of a short-term memory in Drosophila.
    Science. 2000 Apr 28;288(5466):672-5 PMID: 10784450
  43. Cleavage of cohesin by the CD clan protease separin triggers anaphase in yeast.
    Cell. 2000 Oct 27;103(3):375-86 PMID: 11081625
  44. piggyBac-based mosaic screen identifies a postmitotic function for cohesin in regulating developmental axon pruning.
    Dev Cell. 2008 Feb;14(2):227-38 PMID: 18267091
  45. Cell-autonomous requirement of the USP/EcR-B ecdysone receptor for mushroom body neuronal remodeling in Drosophila.
    Neuron. 2000 Dec;28(3):807-18 PMID: 11163268
  46. mau-2 acts cell-autonomously to guide axonal migrations in Caenorhabditis elegans.
    Development. 2004 Dec;131(23):5947-58 PMID: 15539489
  47. Incorporation of Drosophila CID/CENP-A and CENP-C into centromeres during early embryonic anaphase.
    Curr Biol. 2007 Feb 6;17(3):237-43 PMID: 17222555
Article Info
Journal
Developmental cell
Abbr.
Dev Cell
ISSN
1534-5807
DOI
10.1016/j.devcel.2007.12.009
Published
2008-02-00
Pages
239-51
Language
English
Region
United States
NLM ID
101120028
PMCID
PMC2258333
Subset
IM
Grants
Medical Research Council · G0501615 · United Kingdom
External Links
PubMed source DOI: 10.1016/j.devcel.2007.12.009 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2