Patj-KO Mouse

Patj, also known as PALS1-associated tight junction protein, is a core component of the CRB (crumbs) complex. It plays a crucial role in cell polarity, which is an intrinsic property of epithelial cells regulated by scaffold proteins. The CRB complex is part of the dynamic cooperative network of polarity scaffold proteins. Patj is highly conserved throughout evolution and is essential for several important biological events such as embryonic development, cell polarity establishment, and barrier formation. It is also involved in pathways related to tight junction regulation [1,2,3,5,6,7].

In knockout studies, knocking out Patj in epithelial cells leads to tight junction defects, disturbed apical-basal polarity, and impaired lumen formation in three-dimensional cyst assays. This is due to its association with and inhibition of histone deacetylase 7 (HDAC7); downregulation of HDAC7 can restore polarity and lumen formation [3]. In mouse pre-implantation embryos, downregulation of Patj alone slows down blastocyst formation, while depletion of both Patj and its homolog MPDZ impairs blastocyst formation, compromises the expression of trophectoderm-specific transcription factors, and disrupts the CRB and PAR polarity complexes, tight junctions, and actin filaments [5]. In human microvascular endothelial cells, knockdown of Patj causes a complex cell reprogramming involving Notch, TGF-ß, PI3K/Akt, and Hippo signaling, leading to endothelial-to-mesenchymal transition (EndMT) [4].

In conclusion, Patj is vital for maintaining cell polarity, tight junction formation, and is involved in processes like embryonic development and trophectoderm lineage differentiation. Through gene knockout models, its role in stroke prognosis has also been revealed, as Patj downregulation after ischemic stroke promotes EndMT, which may be beneficial for stroke recovery. These findings from model-based research contribute to our understanding of Patj's function in normal biological processes and disease conditions such as stroke [1,4,5].

References:

1. Wang, Wen-Jie, Lyu, Tian-Jie, Li, Zixiao. 2021. Research Progress on PATJ and Underlying Mechanisms Associated with Functional Outcomes After Stroke. In Neuropsychiatric disease and treatment, 17, 2811-2818. doi:10.2147/NDT.S310764. https://pubmed.ncbi.nlm.nih.gov/34471355/

2. Foerster, Elisabeth G, Mukherjee, Tapas, Cabral-Fernandes, Liliane, Girardin, Stephen E, Philpott, Dana J. 2021. How autophagy controls the intestinal epithelial barrier. In Autophagy, 18, 86-103. doi:10.1080/15548627.2021.1909406. https://pubmed.ncbi.nlm.nih.gov/33906557/

3. Fiedler, Julia, Moennig, Thomas, Hinrichs, Johanna H, Nedvetsky, Pavel, Krahn, Michael P. 2023. PATJ inhibits histone deacetylase 7 to control tight junction formation and cell polarity. In Cellular and molecular life sciences : CMLS, 80, 333. doi:10.1007/s00018-023-04994-3. https://pubmed.ncbi.nlm.nih.gov/37878054/

4. Medina-Dols, Aina, Cañellas, Guillem, Capó, Toni, Fernández-Cadenas, Israel, Vives-Bauzá, Cristòfol. 2024. Role of PATJ in stroke prognosis by modulating endothelial to mesenchymal transition through the Hippo/Notch/PI3K axis. In Cell death discovery, 10, 85. doi:10.1038/s41420-024-01857-z. https://pubmed.ncbi.nlm.nih.gov/38368420/

5. Yu, Mingxi, Jiang, Xinlong, Cai, Wenyang, Zhang, Bochuan, Tang, Shuang. 2023. PATJ and MPDZ are required for trophectoderm lineage specification in early mouse embryos. In Reproduction (Cambridge, England), 166, 175-185. doi:10.1530/REP-22-0429. https://pubmed.ncbi.nlm.nih.gov/37318097/

6. Shin, Kunyoo, Straight, Sam, Margolis, Ben. . PATJ regulates tight junction formation and polarity in mammalian epithelial cells. In The Journal of cell biology, 168, 705-11. doi:. https://pubmed.ncbi.nlm.nih.gov/15738264/

7. Michel, Didier, Arsanto, Jean-Pierre, Massey-Harroche, Dominique, Wijnholds, Jan, Le Bivic, André. . PATJ connects and stabilizes apical and lateral components of tight junctions in human intestinal cells. In Journal of cell science, 118, 4049-57. doi:. https://pubmed.ncbi.nlm.nih.gov/16129888/