Drosophila tumor suppressor merlin is essential for mitochondria morphogenesis during spermatogenesis in Drosophila melanogaster

Болоболова, Е. У.; Yudina, O. S.; Дорогова, Н. В.

doi:10.1134/s1990519x11020040

Cited by 3 publications

(2 citation statements)

References 19 publications

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“…S3B). The mRNA levels of the related nuclear genes 42–48 indicated that none but merlin, that has been previously demonstrated to be important for the formation and modification of the nebenkern 47,48 , was significantly downregulated (Fig. S3E).…”

Section: Resultsmentioning

confidence: 68%

Drosophila Pif1A is essential for spermatogenesis and is the homolog of human CCDC157, a gene associated with idiopathic NOA

Yuan

Zheng

et al. 2019

Cell Death Dis

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The dynamic process of spermatogenesis shows little variation between invertebrate models such as Drosophila, and vertebrate models such as mice and rats. In each case, germ stem cells undergo mitotic division to proliferate and then continue, via meiosis, through various stages of elongation and individualization from spermatogonia to spermatid to finally to form mature sperm. Mature sperm are then stored in the seminal vesicles for fertilization. Errors in any of these stages can lead to male infertility. Here, we identify that Drosophila Pif1A acts as a key regulator for sperm individualization. Loss of Pif1A leads to male sterility associated with irregular individualization complex and empty seminal vesicles without mature sperm. Pif1A is highly expressed in the testes of mated male adult flies and the Pif1A protein is expressed at a higher level in male than in female flies. Pif1A is homologous to mammalian coiled-coil domain-containing protein 157 (CCDC157), which is also enriched in the testes of humans and mice. Human CCDC157, with unknown function, was identified to be downregulated in men with idiopathic non-obstructive azoospermia (NOA). We map the function of Drosophila Pif1A during spermatogenesis, showing that Pif1A is essential for spermatide individualization and involved in the regulation of the lipid metabolism genes. Our findings might be applicable for studying the function of CCDC157 in spermatogenesis and other aspects of human male fertility.

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Section: Resultsmentioning

confidence: 68%

Drosophila Pif1A is essential for spermatogenesis and is the homolog of human CCDC157, a gene associated with idiopathic NOA

Yuan

Zheng

et al. 2019

Cell Death Dis

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“…1G function ” on different backgrounds. Furthermore, Merlin has already been described to play a role in Drosophila melanogaster spermatogenesis in regulating mitochondria morphogenesis of maturing sperm [ 46 , 47 ]. Additionally, Giovannini et al reported that accidental deletion of Nf2 in the testis causes infertility in mice [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Merlin Isoforms 1 and 2 Both Act as Tumour Suppressors and Are Required for Optimal Sperm Maturation

et al. 2015

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The tumour suppressor Merlin, encoded by the gene NF2, is frequently mutated in the autosomal dominant disorder neurofibromatosis type II, characterised primarily by the development of schwannoma and other glial cell tumours. However, NF2 is expressed in virtually all analysed human and rodent organs, and its deletion in mice causes early embryonic lethality. Additionally, NF2 encodes for two major isoforms of Merlin of unknown functionality. Specifically, the tumour suppressor potential of isoform 2 remains controversial. In this study, we used Nf2 isoform-specific knockout mouse models to analyse the function of each isoform during development and organ homeostasis. We found that both isoforms carry full tumour suppressor functionality and can completely compensate the loss of the other isoform during development and in most adult organs. Surprisingly, we discovered that spermatogenesis is strictly dependent on the presence of both isoforms. While the testis primarily expresses isoform 1, we noticed an enrichment of isoform 2 in spermatogonial stem cells. Deletion of either isoform was found to cause decreased sperm quality as observed by maturation defects and head/midpiece abnormalities. These defects led to impaired sperm functionality as assessed by decreased sperm capacitation. Thus, we describe spermatogenesis as a new Nf2-dependent process. Additionally, we provide for the first time in vivo evidence for equal tumour suppressor potentials of Merlin isoform 1 and isoform 2.

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Mitochondria, spermatogenesis, and male infertility – An update

2020

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Drosophila tumor suppressor merlin is essential for mitochondria morphogenesis during spermatogenesis in Drosophila melanogaster

Cited by 3 publications

References 19 publications

Drosophila Pif1A is essential for spermatogenesis and is the homolog of human CCDC157, a gene associated with idiopathic NOA

Drosophila Pif1A is essential for spermatogenesis and is the homolog of human CCDC157, a gene associated with idiopathic NOA

Merlin Isoforms 1 and 2 Both Act as Tumour Suppressors and Are Required for Optimal Sperm Maturation

Mitochondria, spermatogenesis, and male infertility – An update

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