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

被引：216

作者：

Pauli, Andrea ^{[1
]}

Althoff, Friederike

Oliveira, Raquel A. ^{[1
]}

Heidmann, Stefan ^{[2
,3
]}

Schuldiner, Oren ^{[4
]}

Lehner, Christian F.

Dickson, Barry J. ^{[5
]}

Nasmyth, Kim ^{[1
]}

机构：

[1] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England

[2] Univ Zurich, Inst Zool, CH-8057 Zurich, Switzerland

[3] Univ Bayreuth, Dept Genet, D-95440 Bayreuth, Germany

[4] Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA

[5] Inst Mol Pathol, A-1030 Vienna, Austria

来源：

DEVELOPMENTAL CELL | 2008年 / 14卷 / 02期

基金：

英国医学研究理事会;

关键词：

SISTER-CHROMATID COHESION; DE-LANGE-SYNDROME; GENE-EXPRESSION; AXONAL MIGRATIONS; TURNING BEHAVIOR; SMC PROTEINS; NIPPED-B; CHROMOSOME; HOMOLOG; LOCALIZATION;

D O I：

10.1016/j.devcel.2007.12.009

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：239 / 251

页数：13

共 47 条

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