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

Andrea Pauli, Friederike Althoff, Raquel A. Oliveira, Stefan Heidmann, Oren Schuldiner, Christian F. Lehner, Barry J. Dickson, Kim Nasmyth*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

225 Citations (Scopus)

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 α 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.
Original languageEnglish
Pages (from-to)239-251
Number of pages13
JournalDevelopmental Cell
Volume14
Issue number2
DOIs
Publication statusPublished - 12 Feb 2008
Externally publishedYes

Keywords

  • Cellcycle
  • Devbio
  • Molneuro

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