Pdlim5, also known as ENH (Enigma homolog), is a cytoskeleton-related cytoplasmic protein with a molecular mass of about 63 KDa. It consists of a PDZ domain at the N-terminus and three LIM domains at the C-terminus. Pdlim5 binds to the cytoskeleton and membrane proteins via its PDZ domain and interacts with various signaling molecules through its LIM domain. It plays a crucial role in regulating cell proliferation, differentiation, and cell fate decision in multiple tissues and cell types, and is involved in pathways like p38-MAPK [1,3].

In rat primary hippocampal neurons, knockdown of Pdlim5 reduces dendrite branching, indicating its role in neuronal dendrite morphology [2,8]. In chicken skeletal muscle satellite cells, interfering with Pdlim5 decreases their proliferation and differentiation, and it functions through the activation of the p38-MAPK signaling pathway [3]. In prenatal stress offspring rats, PDLIM5 can improve depression-like behavior, with methylation of its promoter observed only in male rats [4]. In lung cancer cells, knockdown of PDLIM5 decreases migration and invasion, as it inhibits STUB1-mediated degradation of SMAD3 to promote TGFβ signaling [5]. In pigs, PDLIM5-short, a spliceosome, suppresses myoblast proliferation and differentiation [6]. In neurons, knockdown of either PDLIM5 or PKCε rescues the neuron from PMA-induced growth cone collapse, suggesting PDLIM5 mediates PKCε translocation [7]. Knocking down of PDLIM5 in SH-SY5Y abolishes nicotine-induced upregulation of α7nAChRs, showing its role in regulating α7nAChRs [9].

In conclusion, Pdlim5 is essential for various biological processes such as neuronal development, muscle cell growth, and mental health-related behaviors. Through gene-based functional studies, including knockdown experiments similar to KO/CKO mouse models in different cell types and organisms, its role in diseases like depression and cancer has been revealed, providing insights into potential therapeutic targets.

References:

1. Huang, Xiaolan, Qu, Rongmei, Ouyang, Jun, Zhong, Shizhen, Dai, Jingxing. 2020. An Overview of the Cytoskeleton-Associated Role of PDLIM5. In Frontiers in physiology, 11, 975. doi:10.3389/fphys.2020.00975. https://pubmed.ncbi.nlm.nih.gov/32848888/

2. Srivastava, Yogesh, Donta, Maxsam, Mireles, Lydia L, Waxham, M Neal, McCrea, Pierre D. 2023. Role of a Pdlim5:PalmD complex in directing dendrite morphology. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.08.22.553334. https://pubmed.ncbi.nlm.nih.gov/37662414/

3. He, Haorong, Yin, Huadong, Yu, Xueke, Li, Diyan, Zhu, Qing. 2021. PDLIM5 Affects Chicken Skeletal Muscle Satellite Cell Proliferation and Differentiation via the p38-MAPK Pathway. In Animals : an open access journal from MDPI, 11, . doi:10.3390/ani11041016. https://pubmed.ncbi.nlm.nih.gov/33916517/

4. Lu, Yong, Jiang, Jiguo, Si, Jingfang, Dong, Peng, Zhu, Zhongliang. 2020. PDLIM5 improves depression-like behavior of prenatal stress offspring rats via methylation in male, but not female. In Psychoneuroendocrinology, 115, 104629. doi:10.1016/j.psyneuen.2020.104629. https://pubmed.ncbi.nlm.nih.gov/32171900/

5. Shi, Yueli, Wang, Xinyu, Xu, Zhiyong, Ke, Yuehai, Cheng, Hongqiang. 2020. PDLIM5 inhibits STUB1-mediated degradation of SMAD3 and promotes the migration and invasion of lung cancer cells. In The Journal of biological chemistry, 295, 13798-13811. doi:10.1074/jbc.RA120.014976. https://pubmed.ncbi.nlm.nih.gov/32737199/

6. Fu, Yu, Li, Shixin, Nie, Jingru, Hao, Xin, Zhang, Hao. 2024. Expression of PDLIM5 Spliceosomes and Regulatory Functions on Myogenesis in Pigs. In Cells, 13, . doi:10.3390/cells13080720. https://pubmed.ncbi.nlm.nih.gov/38667334/

7. Ren, Bingyu, Li, Xiubo, Zhang, Jifeng, Duan, Jingjing, Chen, Yuan. 2014. PDLIM5 mediates PKCε translocation in PMA-induced growth cone collapse. In Cellular signalling, 27, 424-35. doi:10.1016/j.cellsig.2014.12.005. https://pubmed.ncbi.nlm.nih.gov/25524223/

8. Srivastava, Yogesh, Donta, Maxsam, Mireles, Lydia L, Waxham, M Neal, McCrea, Pierre D. 2024. Role of a Pdlim5:PalmD complex in directing dendrite morphology. In Frontiers in cellular neuroscience, 18, 1315941. doi:10.3389/fncel.2024.1315941. https://pubmed.ncbi.nlm.nih.gov/38414752/

9. Li, Zi-Lin, Gou, Chen-Yu, Wang, Wen-Hui, Duan, Jing-Jing, Chen, Yuan. 2022. A novel effect of PDLIM5 in α7 nicotinic acetylcholine receptor upregulation and surface expression. In Cellular and molecular life sciences : CMLS, 79, 64. doi:10.1007/s00018-021-04115-y. https://pubmed.ncbi.nlm.nih.gov/35013841/