Proteomic profiling of TBC1 domain family member 21-null sperms reveals the critical roles of TEKT 1 in their tail defects.

Autor: Pan PY; Graduate Institute of Biomedical and Pharmaceutical Science, Fu-Jen Catholic University, New Taipei City, Taiwan., Ke CC; Department of Urology, En Chu Kong Hospital, New Taipei City, Taiwan., Wang YY; Graduate Institute of Biomedical and Pharmaceutical Science, Fu-Jen Catholic University, New Taipei City, Taiwan., Lin YH; Division of Urology, Department of Surgery, Cardinal Tien Hospital, New Taipei City, Taiwan.; Department of Chemistry, Fu Jen Catholic University, New Taipei City, Taiwan., Ku WC; School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan., Au CF; Division of Urology, Department of Surgery, Far Eastern Memorial Hospital, New Taipei City, Taiwan., Chan CC; Department of Obstetrics and Gynecology, Taipei City Hospital, Zhongxing Branch and Branch for Women and Children, Taipei, Taiwan., Huang CY; Gynecologic Cancer Center, Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei, Taiwan., Lin YH; Graduate Institute of Biomedical and Pharmaceutical Science, Fu-Jen Catholic University, New Taipei City, Taiwan.
Jazyk: angličtina
Zdroj: Developmental dynamics : an official publication of the American Association of Anatomists [Dev Dyn] 2024 Nov; Vol. 253 (11), pp. 1024-1035. Date of Electronic Publication: 2024 Jun 01.
DOI: 10.1002/dvdy.716
Abstrakt: 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.
(© 2024 American Association for Anatomy.)
Databáze: MEDLINE
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