Cell-type-specific TEV protease cleavage reveals cohesin functions in Drosophila neurons.
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.
Pauli
Andrea
A
Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
Althoff
Friederike
F
Oliveira
Raquel A
RA
Heidmann
Stefan
S
Schuldiner
Oren
O
Lehner
Christian F
CF
Dickson
Barry J
BJ
Nasmyth
Kim
K
D000818:Animals; D001369:Axons / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D002842:Chromatids / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D020090:Chromosome Segregation; D003712:Dendrites / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism*; D005298:Fertility; D007814:Larva; D008124:Locomotion; D008938:Mitosis; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D009928:Organ Specificity; D011485:Protein Binding; D000097722:Cohesins
D018797:Cell Cycle Proteins; D002794:Choline; D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins; D010450:Endopeptidases; D009687:Nuclear Proteins; D000097722:Cohesins; C410884:vtd protein, Drosophila; C099488:TEV protease