Pkd2l1-KO Mouse

Pkd2l1, also known as TRPP2 or TRPP3, is a member of the transient receptor potential family. It functions as a calcium-permeable non-selective cation channel, regulating intracellular calcium concentration and calcium signaling [3]. Pkd2l1 is involved in pathways such as hedgehog signaling, intestinal development, and sour tasting [4]. It forms heterotetramers with PKD1L3 in a 3:1 stoichiometry [4].

Loss of Pkd2l1 expression in mice ablates primary ciliary maturation and attenuates neuronal high-frequency excitability in hippocampal neurons, leading to seizure susceptibility and autism spectrum disorder-like behavior, suggesting it is a regulator of hippocampal excitability [1]. In zebrafish, loss of the Pkd2l1 channel nearly abolishes calcium activity and single-channel opening in cerebrospinal fluid-contacting neurons (CSF-cNs), and adult pkd2l1 mutant zebrafish develop an exaggerated spine curvature, indicating its role in mechanoception in CSF-cNs and maintenance of spine curvature [2].

In conclusion, Pkd2l1 plays crucial roles in neuronal excitability regulation in the hippocampus, mechanoception in CSF-cNs, and maintenance of spine curvature. Studies using gene knockout models in mice and zebrafish have been instrumental in revealing these functions, with implications for understanding neurological and spinal-related disorders [1,2].

References:

1. Vien, Thuy N, Ta, My C, Kimura, Louise F, Onay, Tuncer, DeCaen, Paul G. 2023. Primary cilia TRP channel regulates hippocampal excitability. In Proceedings of the National Academy of Sciences of the United States of America, 120, e2219686120. doi:10.1073/pnas.2219686120. https://pubmed.ncbi.nlm.nih.gov/37216541/

2. Sternberg, Jenna R, Prendergast, Andrew E, Brosse, Lucie, Delmas, Patrick, Wyart, Claire. 2018. Pkd2l1 is required for mechanoception in cerebrospinal fluid-contacting neurons and maintenance of spine curvature. In Nature communications, 9, 3804. doi:10.1038/s41467-018-06225-x. https://pubmed.ncbi.nlm.nih.gov/30228263/

3. Park, Eunice Yon June, Baik, Julia Young, Kwak, Misun, So, Insuk. 2019. The role of calmodulin in regulating calcium-permeable PKD2L1 channel activity. In The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology, 23, 219-227. doi:10.4196/kjpp.2019.23.3.219. https://pubmed.ncbi.nlm.nih.gov/31080352/

4. Zheng, Wang, Hussein, Shaimaa, Yang, JungWoo, Tang, Jingfeng, Chen, Xing-Zhen. 2015. A novel PKD2L1 C-terminal domain critical for trimerization and channel function. In Scientific reports, 5, 9460. doi:10.1038/srep09460. https://pubmed.ncbi.nlm.nih.gov/25820328/