Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Blotting, Western
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Cell Cycle Proteins / antagonists & inhibitors
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Cell Nucleus / genetics
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Cell Nucleus / metabolism
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Cells, Cultured
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Chromosome Pairing*
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Cytoplasmic Dyneins / genetics
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Cytoplasmic Dyneins / metabolism*
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Cytoskeletal Proteins
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Cytoskeleton / metabolism*
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Female
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HEK293 Cells
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HeLa Cells
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Humans
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Immunoenzyme Techniques
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In Situ Hybridization, Fluorescence
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Male
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Meiosis / physiology*
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Membrane Proteins / antagonists & inhibitors
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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Microtubule-Associated Proteins / antagonists & inhibitors
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / metabolism*
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Microtubules / metabolism
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Molecular Sequence Data
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Nuclear Envelope / metabolism
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Nuclear Proteins / antagonists & inhibitors
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Protein Structure, Tertiary
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RNA, Messenger / genetics
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RNA, Small Interfering / genetics
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Real-Time Polymerase Chain Reaction
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Reverse Transcriptase Polymerase Chain Reaction
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Sequence Homology, Amino Acid
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Spermatocytes / cytology
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Spermatocytes / metabolism
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Telomere / genetics
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Telomere-Binding Proteins / antagonists & inhibitors
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Telomere-Binding Proteins / genetics
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Telomere-Binding Proteins / metabolism*
Substances
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Cell Cycle Proteins
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Cytoskeletal Proteins
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IRAG2 protein, human
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KASH5 protein, mouse
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Membrane Proteins
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Microtubule-Associated Proteins
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Nuclear Proteins
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RNA, Messenger
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RNA, Small Interfering
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SUN1 protein, mouse
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Sun2 protein, mouse
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Telomere-Binding Proteins
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nesprin 4 protein, mouse
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Cytoplasmic Dyneins