Rps6, or ribosomal protein S6, is a crucial protein whose phosphorylation has been extensively studied. It is involved in multiple signaling pathways, most notably the mTORC1 pathway. Rps6 phosphorylation occurs in response to various stimuli and has been associated with important cellular processes such as protein synthesis, cell growth, and proliferation [4]. Genetic models, including gene knockout (KO) and conditional knockout (CKO) mouse models, have been pivotal in elucidating its functions.

In the context of spermatogenesis, studies using the adjudin model (a non-hormonal male contraceptive drug model) have shown that the mTORC1/Rps6 signaling complex plays a significant role. Disrupting the normal function of Rps6 in this model can lead to defects in spermatogenesis, including germ cell exfoliation and aspermatogenesis. This is due to the complex's influence on Sertoli cell-cell adhesion and spermatid-Sertoli cell adhesion, as well as its role in perturbing the cytoskeletal organization of F-actin and microtubules across the seminiferous epithelium [1,5,6,7]. In the wounding response, a mouse model unable to phosphorylate Rps6 shows an initial acceleration of wound closure but impaired healing, indicating that p-Rps6 is a modulator of the healing process [2]. In cholangiocarcinoma, Rps6 deficiency suppresses cell growth by disrupting alternative splicing, as shown by in vivo studies with a phosphorodiamidate morpholino oligomer (V-PMO) targeting Rps6 [3].

In conclusion, Rps6 is essential for multiple biological processes. Its study using KO/CKO mouse models and other in vivo research models has provided insights into its role in spermatogenesis, wound healing, and cancer development. Understanding Rps6's functions can potentially contribute to the development of new strategies for male contraception, wound treatment, and cancer therapy.

References:

1. Wang, Lingling, Li, Linxi, Wu, Xiaolong, Sun, Fei, Cheng, C Yan. 2021. mTORC1/rpS6 and p-FAK-Y407 signaling regulate spermatogenesis: Insights from studies of the adjudin pharmaceutical/toxicant model. In Seminars in cell & developmental biology, 121, 53-62. doi:10.1016/j.semcdb.2021.03.024. https://pubmed.ncbi.nlm.nih.gov/33867214/

2. Ring, Nadja Anneliese Ruth, Dworak, Helene, Bachmann, Barbara, Redl, Heinz, Ogrodnik, Mikolaj. 2023. The p-rpS6-zone delineates wounding responses and the healing process. In Developmental cell, 58, 981-992.e6. doi:10.1016/j.devcel.2023.04.001. https://pubmed.ncbi.nlm.nih.gov/37098351/

3. Fu, Wenkang, Lin, Yanyan, Bai, Mingzhen, Zhang, Wenhua, Meng, Wenbo. 2024. Beyond ribosomal function: RPS6 deficiency suppresses cholangiocarcinoma cell growth by disrupting alternative splicing. In Acta pharmaceutica Sinica. B, 14, 3931-3948. doi:10.1016/j.apsb.2024.06.028. https://pubmed.ncbi.nlm.nih.gov/39309509/

4. Meyuhas, Oded. 2015. Ribosomal Protein S6 Phosphorylation: Four Decades of Research. In International review of cell and molecular biology, 320, 41-73. doi:10.1016/bs.ircmb.2015.07.006. https://pubmed.ncbi.nlm.nih.gov/26614871/

5. Wu, Siwen, Yan, Ming, Li, Linxi, Lian, Qingquan, Cheng, C Yan. 2019. mTORC1/rpS6 and spermatogenic function in the testis-insights from the adjudin model. In Reproductive toxicology (Elmsford, N.Y.), 89, 54-66. doi:10.1016/j.reprotox.2019.07.002. https://pubmed.ncbi.nlm.nih.gov/31278979/

6. Li, Zhen-Fang, Qi, Hong-Yu, Wang, Jia-Ming, Tan, Fu-Qing, Yang, Wan-Xi. 2023. mTORC1/rpS6 and mTORC2/PKC regulate spermatogenesis through Arp3-mediated actin microfilament organization in Eriocheir sinensis. In Cell and tissue research, 393, 559-575. doi:10.1007/s00441-023-03795-1. https://pubmed.ncbi.nlm.nih.gov/37328709/

7. Yan, Ming, Li, Linxi, Mao, Baiping, Ge, Renshan, Cheng, C Yan. 2019. mTORC1/rpS6 signaling complex modifies BTB transport function: an in vivo study using the adjudin model. In American journal of physiology. Endocrinology and metabolism, 317, E121-E138. doi:10.1152/ajpendo.00553.2018. https://pubmed.ncbi.nlm.nih.gov/31112404/