Strip1-KO Mouse

Strip1, or striatin-interacting protein 1, is a core component of the striatin-interacting phosphatases and kinases (STRIPAK) complex. This complex integrates diverse cellular signals in the Hippo pathway, regulating cell proliferation and survival [6]. STRIPAK, with Strip1 as a key part, is evolutionarily conserved and involved in various biological processes such as embryogenesis, development, and circadian rhythms [2]. Genetic models like zebrafish, C. elegans, and mice have been crucial in studying Strip1's functions.

In zebrafish, loss of Strip1 causes defects in inner retina development. RGCs undergo apoptosis shortly after birth, leading to disorganized inner plexiform layer (IPL) formation as other neurons invade the degenerating RGC layer. Mechanistically, Strip1 interacts with Strn3, and both suppress Jun-mediated apoptosis in RGCs [1]. In mouse cochlear hair cells, Strip1 expression increases with age, and homozygous knockout is embryonic lethal, suggesting its importance in hair cell development and maturation [2]. In C. elegans, FARL-11 (STRIP1/2) is required for sarcomere and sarcoplasmic reticulum organization, and missense mutations in farl-11 result in sarcomere disorganization and SR disruption [3,4]. In mouse embryos, Strip1-null mutants arrest development at mid-gestation due to disrupted mesoderm migration, associated with decreased cell spreading, abnormal focal adhesions, and actin cytoskeleton changes [5]. In cancer cells, loss of Strip1 in MDA-MB-231 cells leads to cell cycle arrest and decreased proliferation via induction of p21 and p27, but cells may escape therapy-induced senescence upon low-dosage chemotherapy [7].

In summary, Strip1 plays essential roles in multiple biological processes including neural circuit formation, cochlear hair cell development, muscle structure organization, embryonic mesoderm migration, and cancer cell behavior. Studies using gene knockout models in various organisms, especially mice, have significantly contributed to understanding its functions in these processes and potential implications in diseases like glaucoma and cancer [1,2,5,7].

References:

1. Ahmed, Mai, Kojima, Yutaka, Masai, Ichiro. 2022. Strip1 regulates retinal ganglion cell survival by suppressing Jun-mediated apoptosis to promote retinal neural circuit formation. In eLife, 11, . doi:10.7554/eLife.74650. https://pubmed.ncbi.nlm.nih.gov/35314028/

2. Zhang, Shasha, Dong, Ying, Qiang, Ruiying, Chen, Jie, Chai, Renjie. 2021. Characterization of Strip1 Expression in Mouse Cochlear Hair Cells. In Frontiers in genetics, 12, 625867. doi:10.3389/fgene.2021.625867. https://pubmed.ncbi.nlm.nih.gov/33889175/

3. Martin, Sterling C T, Qadota, Hiroshi, Oberhauser, Andres F, Hardin, Jeff, Benian, Guy M. 2023. FARL-11 (STRIP1/2) is required for sarcomere and sarcoplasmic reticulum organization in C. elegans. In Molecular biology of the cell, 34, ar86. doi:10.1091/mbc.E23-03-0083. https://pubmed.ncbi.nlm.nih.gov/37314837/

4. Martin, Sterling C T, Qadota, Hiroshi, Oberhauser, Andres F, Hardin, Jeff, Benian, Guy M. 2023. FARL-11 (STRIP1/2) is Required for Sarcomere and Sarcoplasmic Reticulum Organization in C. elegans. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.03.05.531173. https://pubmed.ncbi.nlm.nih.gov/36945551/

5. Bazzi, Hisham, Soroka, Ekaterina, Alcorn, Heather L, Anderson, Kathryn V. 2017. STRIP1, a core component of STRIPAK complexes, is essential for normal mesoderm migration in the mouse embryo. In Proceedings of the National Academy of Sciences of the United States of America, 114, E10928-E10936. doi:10.1073/pnas.1713535114. https://pubmed.ncbi.nlm.nih.gov/29203676/

6. Jeong, Byung-Cheon, Bae, Sung Jun, Ni, Lisheng, Bai, Xiao-Chen, Luo, Xuelian. 2021. Cryo-EM structure of the Hippo signaling integrator human STRIPAK. In Nature structural & molecular biology, 28, 290-299. doi:10.1038/s41594-021-00564-y. https://pubmed.ncbi.nlm.nih.gov/33633399/

7. Rodriguez-Cupello, Carmen, Dam, Monica, Serini, Laura, García-Mariscal, Alberto, Madsen, Chris D. 2020. The STRIPAK Complex Regulates Response to Chemotherapy Through p21 and p27. In Frontiers in cell and developmental biology, 8, 146. doi:10.3389/fcell.2020.00146. https://pubmed.ncbi.nlm.nih.gov/32258031/