title: Nuclear pore complex evolution: a trypanosome Mlp analogue functions in chromosomal segregation but lacks transcriptional barrier activity.
abstract: The nuclear pore complex (NPC) has dual roles in nucleocytoplasmic transport and chromatin organization. In many eukaryotes the coiled-coil Mlp/Tpr proteins of the NPC nuclear basket have specific functions in interactions with chromatin and defining specialized regions of active transcription, whereas Mlp2 associates with the mitotic spindle/NPC in a cell cycle-dependent manner. We previously identified two putative Mlp-related proteins in African trypanosomes, TbNup110 and TbNup92, the latter of which associates with the spindle. We now provide evidence for independent ancestry for TbNup92/TbNup110 and Mlp/Tpr proteins. However, TbNup92 is required for correct chromosome segregation, with knockout cells exhibiting microaneuploidy and lowered fidelity of telomere segregation. Further, TbNup92 is intimately associated with the mitotic spindle and spindle anchor site but apparently has minimal roles in control of gene transcription, indicating that TbNup92 lacks major barrier activity. TbNup92 therefore acts as a functional analogue of Mlp/Tpr proteins, and, together with the lamina analogue NUP-1, represents a cohort of novel proteins operating at the nuclear periphery of trypanosomes, uncovering complex evolutionary trajectories for the NPC and nuclear lamina.
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 5EH, United Kingdom The Rockefeller University, New York, NY 10021 Seattle Biomedical Research Institute and Institute for Systems Biology, Seattle, WA 98109 Department of Computer Science and Information Engineering, National Cheng Kung University, Tainan City 701, Taiwan Department of Plant Sciences, University of Oxford, Oxford OX1 4JP, United Kingdom.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Holden
authors.forename: Ludek
authors.initials: L
authors.lastname: Koreny
authors.forename: Samson
authors.initials: S
authors.lastname: Obado
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Ratushny
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Chen
authors.forename: Jung-Hsien
authors.initials: JH
authors.lastname: Chiang
authors.forename: Steven
authors.initials: S
authors.lastname: Kelly
authors.forename: Brian T
authors.initials: BT
authors.lastname: Chait
authors.forename: John D
authors.initials: JD
authors.lastname: Aitchison
authors.forename: Michael P
authors.initials: MP
authors.lastname: Rout
authors.forename: Mark C
authors.initials: MC
authors.lastname: Field
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D020090:Chromosome Segregation; D019143:Evolution, Molecular; D059565:G2 Phase Cell Cycle Checkpoints; D008938:Mitosis; D022022:Nuclear Pore / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014346:Trypanosoma brucei brucei / Q000166:cytology / Q000378:metabolism*
chemical_list: D028861:Nuclear Pore Complex Proteins; D015800:Protozoan Proteins