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1.
DNA Cell Biol ; 29(9): 487-98, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20491580

ABSTRACT

Temporal coordination of meiosis with spermatid morphogenesis is crucial for successful generation of mature sperm cells. We identified a recessive male sterile Drosophila melanogaster mutant, mitoshell, in which events of spermatid morphogenesis are initiated too early, before meiotic onset. Premature mitochondrial aggregation and fusion lead to an aberrant mitochondrial shell around premeiotic nuclei. Despite successful meiotic karyokinesis, improper mitochondrial localization in mitoshell testes is associated with defective astral central spindles and a lack of contractile rings, leading to meiotic cytokinesis failure. We mapped and cloned the mitoshell gene and found that it encodes a novel protein with a bromodomain-related region. It is conserved in some insect lineages. Bromodomains typically bind to histone acetyl-lysine residues and therefore are often associated with chromatin. The Mitoshell bromodomain-related region is predicted to have an alpha helical structure similar to that of bromodomains, but not all the crucial residues in the ligand-binding loops are conserved. We speculate that Mitoshell may participate in transcriptional regulation of spermatogenesis-specific genes, though perhaps with different ligand specificity compared to traditional bromodomains.


Subject(s)
Chromosomal Proteins, Non-Histone/chemistry , Chromosomal Proteins, Non-Histone/metabolism , Cytokinesis , Drosophila Proteins/chemistry , Drosophila Proteins/metabolism , Drosophila melanogaster/cytology , Drosophila melanogaster/metabolism , Insect Proteins/chemistry , Insect Proteins/metabolism , Meiosis , Spermatogenesis , Amino Acid Sequence , Animals , Chromosomal Proteins, Non-Histone/genetics , Cloning, Molecular , Conserved Sequence , Cytokinesis/genetics , Drosophila Proteins/genetics , Drosophila melanogaster/genetics , Drosophila melanogaster/growth & development , Female , Genes, Insect/genetics , Infertility, Male/genetics , Insect Proteins/genetics , Male , Meiosis/genetics , Mitochondria/metabolism , Molecular Sequence Data , Mutation , Protein Structure, Tertiary , Spermatogenesis/genetics , Testis/growth & development , Testis/metabolism
2.
Fly (Austin) ; 1(1): 38-46, 2007.
Article in English | MEDLINE | ID: mdl-18690063

ABSTRACT

Mitochondria undergo dramatic rearrangement during Drosophila spermatogenesis. In wild type testes, the many small mitochondria present in pre-meiotic spermatocytes later aggregate, fuse, and interwrap in post-meiotic haploid spermatids to form the spherical Nebenkern, whose two giant mitochondrial compartments later unfurl and elongate beside the growing flagellar axoneme. Drp1 encodes a dynamin-related protein whose homologs in many organisms mediate mitochondrial fission and whose Drosophila homolog is known to govern mitochondrial morphology in neurons. The milton gene encodes an adaptor protein that links mitochondria with kinesin and that is required for mitochondrial transport in Drosophila neurons. To determine the roles of Drp1 and Milton in spermatogenesis, we used the FLP-FRT mitotic recombination system to generate spermatocytes homozygous for mutations in either gene in an otherwise heterozygous background. We found that absence of Drp1 leads to abnormal clustering of mitochondria in mature primary spermatocytes and aberrant unfurling of the mitochondrial derivatives in early Drp1 spermatids undergoing axonemal elongation. In milton spermatocytes, mitochondria are distributed normally; however, after meiosis, the Nebenkern is not strongly anchored to the nucleus, and the mitochondrial derivatives do not elongate properly. Our work defines specific functions for Drp1 and Milton in the anchoring, unfurling, and elongation of mitochondria during sperm formation.


Subject(s)
Cytoskeletal Proteins/physiology , Drosophila Proteins/physiology , Drosophila/physiology , GTP-Binding Proteins/physiology , Mitochondria/physiology , Nerve Tissue Proteins/physiology , Spermatogenesis , Animals , Female , Male , Meiosis , Mosaicism , Mutation , Spermatids/pathology , Spermatocytes/pathology , Testis/physiology
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