TBC1结构域家族成员21缺失精子的蛋白质组分析揭示了TEKT 1在精子尾部缺陷中的关键作用。

IF 2 3区 生物学 Q2 ANATOMY & MORPHOLOGY
Pei-Yi Pan, Chih-Chun Ke, Ya-Yun Wang, Yu-Hua Lin, Wei-Chi Ku, Chin-Fong Au, Chying-Chyuan Chan, Chia-Yen Huang, Ying-Hung Lin
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引用次数: 0

摘要

背景:约有 7% 的雄性动物表现出生育能力下降;然而,其中涉及的调控基因和途径在很大程度上仍不为人所知。TBC1结构域家族成员21(TBC1D21)含有一个保守的RabGAP催化结构域,可诱导GDP/GTP交换,通过与微管相互作用使Rabs失活。我们以前曾报道过,Tbc1d21 缺失的小鼠表现出严重的精子尾部缺陷,轴突被破坏,而且 TBC1D21 与 RAB10 相互作用。然而,Tbc1d21缺失导致精子尾部缺陷的病理机制仍不清楚:结果:使用蛋白质组学方法对野生型小鼠和 Tbc1d21 基因缺失小鼠的精子进行了比较分析。结果:利用蛋白质组学分析方法对野生型和 Tbc1d21 缺失型小鼠的精子进行了比较分析,共鉴定出 1600 多种蛋白质,其中 15 种蛋白质在 Tbc1d21 缺失型精子中显著上调。值得注意的是,在Tbc1d21-/-无效精子中,几种属于对稳定纤毛和鞭毛微管结构至关重要的中间丝类型的tektin(TEKT)家族蛋白被显著上调。我们还发现 TBC1D21 与 TEKT1 相互作用。此外,在精子尾部形成过程中,TEKT1与RAB10共定位。最后,我们发现TBC1d21-null精子的中段区域出现了TEKT1的异常聚集,并伴有轴丝结构的破坏:这些结果表明,在精子尾部形成过程中,TBC1D21会调节TEKTs蛋白在轴丝运输系统中的定位。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Proteomic profiling of TBC1 domain family member 21-null sperms reveals the critical roles of TEKT 1 in their tail defects

Background

Approximately 7% of the males exhibit reduced fertility; however, the regulatory genes and pathways involved remain largely unknown. TBC1 domain family member 21 (TBC1D21) contains a conserved RabGAP catalytic domain that induces GDP/GTP exchange to inactivate Rabs by interacting with microtubules. We previously reported that Tbc1d21-null mice exhibit severe sperm tail defects with a disrupted axoneme, and that TBC1D21 interacts with RAB10. However, the pathological mechanisms underlying the Tbc1d21 loss-induced sperm tail defects remain unknown.

Results

Murine sperm from wild-type and Tbc1d21-null mice were comparatively analyzed using proteomic assays. Over 1600 proteins were identified, of which 15 were significantly up-regulated in Tbc1d21-null sperm. Notably, several tektin (TEKT) family proteins, belonging to a type of intermediate filament critical for stabilizing the microtubular structure of cilia and flagella, were significantly up-regulated in Tbc1d21−/− sperm. We also found that TBC1D21 interacts with TEKT1. In addition, TEKT1 co-localized with RAB10 during sperm tail formation. Finally, we found Tbc1d21-null sperm exhibited abnormal accumulation of TEKT1 in the midpiece region, accompanied by disrupted axonemal structures.

Conclusions

These results reveal that TBC1D21 modulates TEKTs protein localization in the axonemal transport system during sperm tail formation.

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来源期刊
Developmental Dynamics
Developmental Dynamics 生物-发育生物学
CiteScore
5.10
自引率
8.00%
发文量
116
审稿时长
3-8 weeks
期刊介绍: Developmental Dynamics, is an official publication of the American Association for Anatomy. This peer reviewed journal provides an international forum for publishing novel discoveries, using any model system, that advances our understanding of development, morphology, form and function, evolution, disease, stem cells, repair and regeneration.
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