Plxnb1, a member of the plexin family receptors, serves as the receptor for semaphorin 4D (Sema4D) and is involved in semaphorin/plexin signaling. This signaling pathway is crucial for various biological processes such as cell migration, axon guidance, and immune cell regulation [1,2,3,5,6]. Genetic models, especially knockout mouse models, have been valuable in studying Plxnb1's functions.

In a study on idiopathic hypogonadotropic hypogonadism (IHH), six rare sequence variants in PLXNB1 were identified in normosmic IHH patients. Functional analysis of the p.R1031H variant showed reduced membrane expression and impaired migration in GnRH cells compared to the wild-type, suggesting its role in IHH etiology [1]. In pediatric bipolar disorder (PBD), a rare homozygous loss-of-function PLXNB1 variant was found to cause neurite outgrowth deficits in patient-derived cortical neurons, indicating its potential role in mood dysregulation-related disorders [4]. In breast cancer, PLXNB1-deficient mice showed reduced primary tumor growth and metastatic dissemination, with a switch in tumor-associated macrophages to a pro-inflammatory M1 phenotype and enhanced CD8+ T lymphocyte infiltration, highlighting its role in the tumor microenvironment [5].

In conclusion, Plxnb1 is essential for multiple biological processes and its dysregulation is implicated in various diseases. Gene knockout models, especially in mice, have been instrumental in revealing its role in diseases like IHH, PBD, and breast cancer, providing insights into disease mechanisms and potential therapeutic targets.

References:

1. Welch, Bradley A, Cho, Hyun-Ju, Ucakturk, Seyit Ahmet, Wray, Susan, Topaloglu, A Kemal. 2022. PLXNB1 mutations in the etiology of idiopathic hypogonadotropic hypogonadism. In Journal of neuroendocrinology, 34, e13103. doi:10.1111/jne.13103. https://pubmed.ncbi.nlm.nih.gov/35170806/

2. Clark, Iain C, Gutiérrez-Vázquez, Cristina, Wheeler, Michael A, Prat, Alexandre, Quintana, Francisco J. . Barcoded viral tracing of single-cell interactions in central nervous system inflammation. In Science (New York, N.Y.), 372, . doi:10.1126/science.abf1230. https://pubmed.ncbi.nlm.nih.gov/33888612/

3. Xuan, Zixue, Zhang, Yuan, Li, Dan, Huang, Ping, Shi, Jiana. . PLXNB1/SEMA4D signals mediate interactions between malignant epithelial and immune cells to promote colorectal cancer liver metastasis. In Journal of cellular and molecular medicine, 28, e70142. doi:10.1111/jcmm.70142. https://pubmed.ncbi.nlm.nih.gov/39443302/

4. Yang, Guang, Ullah, H M Arif, Parker, Ethan, Yandell, Mark, Shcheglovitov, Alex. 2023. Neurite outgrowth deficits caused by rare PLXNB1 mutation in pediatric bipolar disorder. In Molecular psychiatry, 28, 2525-2539. doi:10.1038/s41380-023-02035-w. https://pubmed.ncbi.nlm.nih.gov/37032361/

5. Franzolin, Giulia, Brundu, Serena, Cojocaru, Carina F, Tamagnone, Luca, Giraudo, Enrico. . PlexinB1 Inactivation Reprograms Immune Cells in the Tumor Microenvironment, Inhibiting Breast Cancer Growth and Metastatic Dissemination. In Cancer immunology research, 12, 1286-1301. doi:10.1158/2326-6066.CIR-23-0289. https://pubmed.ncbi.nlm.nih.gov/38874583/

6. Wu, Jie-Hong, Li, Ya-Nan, Chen, An-Qi, Yue, Zhen-Yu, Hu, Bo. 2020. Inhibition of Sema4D/PlexinB1 signaling alleviates vascular dysfunction in diabetic retinopathy. In EMBO molecular medicine, 12, e10154. doi:10.15252/emmm.201810154. https://pubmed.ncbi.nlm.nih.gov/31943789/