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Bi-allelic mutation in Fsip1 impairs acrosome vesicle formation and attenuates flagellogenesis in mice

Fibrous sheath interacting protein 1 (Fsip1) is a cytoskeletal structural protein of the sperm flagellar proteome. A few studies have reported that it plays a vital role in the tumorigenesis and cancer progression. However, little is known about the role of Fsip1 in spermatogenesis and mammalian spe...

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Autores principales: Gamallat, Yaser, Fang, Xiang, Mai, Hanran, Liu, Xiaonan, Li, Hong, Zhou, Pei, Han, Dingding, Zheng, Shuxin, Liao, Caihua, Yang, Miaomiao, Li, Yan, Zuo, Liandong, Sun, Ling, Hu, Hao, Li, Na
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099781/
https://www.ncbi.nlm.nih.gov/pubmed/33901807
http://dx.doi.org/10.1016/j.redox.2021.101969
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author Gamallat, Yaser
Fang, Xiang
Mai, Hanran
Liu, Xiaonan
Li, Hong
Zhou, Pei
Han, Dingding
Zheng, Shuxin
Liao, Caihua
Yang, Miaomiao
Li, Yan
Zuo, Liandong
Sun, Ling
Hu, Hao
Li, Na
author_facet Gamallat, Yaser
Fang, Xiang
Mai, Hanran
Liu, Xiaonan
Li, Hong
Zhou, Pei
Han, Dingding
Zheng, Shuxin
Liao, Caihua
Yang, Miaomiao
Li, Yan
Zuo, Liandong
Sun, Ling
Hu, Hao
Li, Na
author_sort Gamallat, Yaser
collection PubMed
description Fibrous sheath interacting protein 1 (Fsip1) is a cytoskeletal structural protein of the sperm flagellar proteome. A few studies have reported that it plays a vital role in the tumorigenesis and cancer progression. However, little is known about the role of Fsip1 in spermatogenesis and mammalian sperm flagellogenesis. Fsip1 protein showed the highest expression in round spermatids, and was translocated from nucleus to the anterior region of the elongating spermatid head. To investigate its role we constructed homozygous Fsip1 null (Fsip1(−/−)) mice. We found that the homozygous Fsip1(−/−) mutant mice were infertile, with a low sperm count and impaired motility. Interestingly, a subtle phenotype characterized by abnormal head shape, and flagella deformities was observed in the sperm of Fsip1(−/−) mutant mice similar to the partial globozoospermia phenotype. Electron microscopy analysis of Fsip1(−/−) sperm revealed abnormal accumulation of mitochondria, disrupted axoneme and retained cytoplasm. Testicular sections showed increased cytoplasmic vacuoles in the elongated spermatid of Fsip1(–/–)mice, which indicated an intraflagellar transport (IFT) defect. Using proteomic approaches, we characterized the cellular components and the mechanism underlying this subtle phenotype. Our result indicated that Fsip1(–/–)downregulates the formation of acrosomal membrane and vesicles proteins, intraflagellar transport particles B, and sperm flagellum components. Our results suggest that Fsip1 is essential for normal spermiogenesis, and plays an essential role in the acrosome biogenesis and flagellogenesis by attenuating intraflagellar transport proteins.
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spelling pubmed-80997812021-05-13 Bi-allelic mutation in Fsip1 impairs acrosome vesicle formation and attenuates flagellogenesis in mice Gamallat, Yaser Fang, Xiang Mai, Hanran Liu, Xiaonan Li, Hong Zhou, Pei Han, Dingding Zheng, Shuxin Liao, Caihua Yang, Miaomiao Li, Yan Zuo, Liandong Sun, Ling Hu, Hao Li, Na Redox Biol Research Paper Fibrous sheath interacting protein 1 (Fsip1) is a cytoskeletal structural protein of the sperm flagellar proteome. A few studies have reported that it plays a vital role in the tumorigenesis and cancer progression. However, little is known about the role of Fsip1 in spermatogenesis and mammalian sperm flagellogenesis. Fsip1 protein showed the highest expression in round spermatids, and was translocated from nucleus to the anterior region of the elongating spermatid head. To investigate its role we constructed homozygous Fsip1 null (Fsip1(−/−)) mice. We found that the homozygous Fsip1(−/−) mutant mice were infertile, with a low sperm count and impaired motility. Interestingly, a subtle phenotype characterized by abnormal head shape, and flagella deformities was observed in the sperm of Fsip1(−/−) mutant mice similar to the partial globozoospermia phenotype. Electron microscopy analysis of Fsip1(−/−) sperm revealed abnormal accumulation of mitochondria, disrupted axoneme and retained cytoplasm. Testicular sections showed increased cytoplasmic vacuoles in the elongated spermatid of Fsip1(–/–)mice, which indicated an intraflagellar transport (IFT) defect. Using proteomic approaches, we characterized the cellular components and the mechanism underlying this subtle phenotype. Our result indicated that Fsip1(–/–)downregulates the formation of acrosomal membrane and vesicles proteins, intraflagellar transport particles B, and sperm flagellum components. Our results suggest that Fsip1 is essential for normal spermiogenesis, and plays an essential role in the acrosome biogenesis and flagellogenesis by attenuating intraflagellar transport proteins. Elsevier 2021-04-16 /pmc/articles/PMC8099781/ /pubmed/33901807 http://dx.doi.org/10.1016/j.redox.2021.101969 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Gamallat, Yaser
Fang, Xiang
Mai, Hanran
Liu, Xiaonan
Li, Hong
Zhou, Pei
Han, Dingding
Zheng, Shuxin
Liao, Caihua
Yang, Miaomiao
Li, Yan
Zuo, Liandong
Sun, Ling
Hu, Hao
Li, Na
Bi-allelic mutation in Fsip1 impairs acrosome vesicle formation and attenuates flagellogenesis in mice
title Bi-allelic mutation in Fsip1 impairs acrosome vesicle formation and attenuates flagellogenesis in mice
title_full Bi-allelic mutation in Fsip1 impairs acrosome vesicle formation and attenuates flagellogenesis in mice
title_fullStr Bi-allelic mutation in Fsip1 impairs acrosome vesicle formation and attenuates flagellogenesis in mice
title_full_unstemmed Bi-allelic mutation in Fsip1 impairs acrosome vesicle formation and attenuates flagellogenesis in mice
title_short Bi-allelic mutation in Fsip1 impairs acrosome vesicle formation and attenuates flagellogenesis in mice
title_sort bi-allelic mutation in fsip1 impairs acrosome vesicle formation and attenuates flagellogenesis in mice
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099781/
https://www.ncbi.nlm.nih.gov/pubmed/33901807
http://dx.doi.org/10.1016/j.redox.2021.101969
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