title: The GTPase SPAG-1 orchestrates meiotic program by dictating meiotic resumption and cytoskeleton architecture in mouse oocytes.
abstract: In mammals, a finite population of oocytes is generated during embryogenesis, and proper oocyte meiotic divisions are crucial for fertility. Sperm-associated antigen 1 (SPAG-1) has been implicated in infertility and tumorigenesis; however, its relevance in cell cycle programs remains rudimentary. Here we explore a novel role of SPAG-1 during oocyte meiotic progression. SPAG-1 associated with meiotic spindles and its depletion severely compromised M-phase entry (germinal vesicle breakdown [GVBD]) and polar body extrusion. The GVBD defect observed was due to an increase in intraoocyte cAMP abundance and decrease in ATP production, as confirmed by the activation of AMP-dependent kinase (AMPK). SPAG-1 RNA interference (RNAi)-elicited defective spindle morphogenesis was evidenced by the dysfunction of γ-tubulin, which resulted from substantially reduced phosphorylation of MAPK and irregularly dispersed distribution of phospho-MAPK around spindles instead of concentration at spindle poles. Significantly, actin expression abruptly decreased and formation of cortical granule-free domains, actin caps, and contractile ring disrupted by SPAG-1 RNAi. In addition, the spindle assembly checkpoint remained functional upon SPAG-1 depletion. The findings broaden our knowledge of SPAG-1, showing that it exerts a role in oocyte meiotic execution via its involvement in AMPK and MAPK signaling pathways.
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Education Ministry of China, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Chunjie
authors.initials: C
authors.lastname: Huang
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Education Ministry of China, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Education Ministry of China, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Faheem Ahmed
authors.initials: FA
authors.lastname: Khan
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Education Ministry of China, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Jiao
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Education Ministry of China, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Kaifeng
authors.initials: K
authors.lastname: Guan
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Education Ministry of China, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China lijunhuo@yahoo.com.
authors.forename: Lijun
authors.initials: L
authors.lastname: Huo
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000235:genetics / Q000378:metabolism*; D005260:Female; D019204:GTP-Binding Proteins; D059566:M Phase Cell Cycle Checkpoints / Q000502:physiology; D020935:MAP Kinase Signaling System; D008540:Meiosis / Q000502:physiology; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D059705:Polar Bodies / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
chemical_list: D000199:Actins; D000941:Antigens; D011506:Proteins; C404906:Spag1 protein, mouse; D014404:Tubulin; D019204:GTP-Binding Proteins