A mammalian KASH domain protein coupling meiotic chromosomes to the cytoskeleton.
Chromosome pairing is an essential meiotic event that ensures faithful haploidization and recombination of the genome. Pairing of homologous chromosomes is facilitated by telomere-led chromosome movements and formation of a meiotic bouquet, where telomeres cluster to one pole of the nucleus. In metazoans, telomere clustering is dynein and microtubule dependent and requires Sun1, an inner nuclear membrane protein. Here we provide a functional analysis of KASH5, a mammalian dynein-binding protein of the outer nuclear membrane that forms a meiotic complex with Sun1. This protein is related to zebrafish futile cycle (Fue), a nuclear envelope (NE) constituent required for pronuclear migration. Mice deficient in this Fue homologue are infertile. Males display meiotic arrest in which pairing of homologous chromosomes fails. These findings demonstrate that telomere attachment to the NE is insufficient to promote pairing and that telomere attachment sites must be coupled to cytoplasmic dynein and the microtubule system to ensure meiotic progression.
Laborotory of Nuclear Dynamics and Architecture, 2 Laboratory of Developmental and Regenerative Biology, and 3 IMB Microscopy Unit, Institute of Medical Biology, 8A Biomedical Grove, Immunos, Singapore 138648.
Henning F
HF
Horn
Dae In
DI
Kim
Graham D
GD
Wright
Esther Sook Miin
ES
Wong
Colin L
CL
Stewart
Brian
B
Burke
Kyle J
KJ
Roux
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D023902:Chromosome Pairing; D056445:Cytoplasmic Dyneins / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000378:metabolism*; D005260:Female; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008540:Meiosis / Q000502:physiology*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D009685:Nuclear Envelope / Q000378:metabolism; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013090:Spermatocytes / Q000166:cytology / Q000378:metabolism; D016615:Telomere / Q000235:genetics; D034501:Telomere-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C486311:IRAG2 protein, human; C575644:KASH5 protein, mouse; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C464932:SUN1 protein, mouse; C520338:Sun2 protein, mouse; D034501:Telomere-Binding Proteins; C539339:nesprin 4 protein, mouse; D056445:Cytoplasmic Dyneins