The role of Drosophila Merlin in spermatogenesis

Abstract

BackgroundDrosophila Merlin, the homolog of the human Neurofibromatosis 2 (NF2) gene, is important for the regulation of cell proliferation and receptor endocytosis. Male flies carrying a Mer3 allele, a missense mutation (Met177→Ile) in the Merlin gene, are viable but sterile; however, the cause of sterility is unknown.ResultsTestis examination reveals that hemizygous Mer3 mutant males have small seminal vesicles that contain only a few immotile sperm. By cytological and electron microscopy analyses of the Mer3, Mer4 (Gln170→stop), and control testes at various stages of spermatogenesis, we show that Merlin mutations affect meiotic cytokinesis of spermatocytes, cyst polarization and nuclear shaping during spermatid elongation, and spermatid individualization. We also demonstrate that the lethality and sterility phenotype of the Mer4 mutant is rescued by the introduction of a wild-type Merlin gene. Immunostaining demonstrates that the Merlin protein is redistributed to the area associated with the microtubules of the central spindle in telophase and its staining is less in the region of the contractile ring during meiotic cytokinesis. At the onion stage, Merlin is concentrated in the Nebenkern of spermatids, and this mitochondrial localization is maintained throughout sperm formation. Also, Merlin exhibits punctate staining in the acrosomal region of mature sperm.ConclusionMerlin mutations affect spermatogenesis at multiple stages. The Merlin protein is dynamically redistributed during meiosis of spermatocytes and is concentrated in the Nebenkern of spermatids. Our results demonstrated for the first time the mitochondrial localization of Merlin and suggest that Merlin may play a role in mitochondria formation and function during spermatogenesis.

Microtubule-mediated transport of the tumor-suppressor protein Merlin and its mutants

“…Our results showing that K70E colocalizes with WT Merlin in immotile particles agree with previous studies demonstrating that the subcellular distribution of the NF2-mutants of Merlin with FERM domain abnormalities was primarily perinuclear, without accumulation at the membrane (35,36). These results clearly indicate a defect in protein trafficking with the potential to affect membrane-cytoskeleton signaling and block growth-inhibiting responses, leading to tumor development.…”

Roles of histone H3K9 methyltransferases during Drosophila spermatogenesis

“…Then, the flagella axonema elongates and the cystic bulge is pushed backward for sweeping the cytoplasm and organelles out of the sperm flagella in the so-called elongation stage (Fuller 1993). Then the heads of spermatids containing nuclei elongate and further condense by replacing histones with protamines to complete spermatogenesis in the canoe stage (Rathke et al 2007, Dorogova et al 2008.…”

DrosophilaPast1 is involved in endocytosis and is required for germline development and survival of the adult fly

“…Interestingly, other fly mutants defective in endocytosis also display male or female sterility, and the latter is associated with abnormal oogenesis, e.g. yolkless, quitPK61, stillPS34, Merlin and clathrinheavy-chain 4 (Bazinet et al, 1993;DiMario and Mahowald, 1987;Dorogova et al, 2008;Gutzeit and Arendt, 1994), and mutants in the C. elegans EHD ortholog rme-1 failed to recycle yolk receptors . These results highlight the importance of Past1, and endocytosis, in development and maturation of the germlines.…”