Inka2, also known as Inka box actin regulator 2, is a gene that plays a crucial role in regulating actin dynamics. It is involved in the Pak4-Cofilin signaling cascade, which is central to the actin filaments. Inka2 is known to be an endogenous inhibitor of Pak4, a serine/threonine-protein kinase that links Rho GTPases to control actin polymerization. This regulation of actin dynamics is essential for various physiological processes such as cell migration, dendritic spine development, and focal-adhesion dynamics [1,2,3,4,5].

Conditional knockout (CKO) mice of the Inka2 gene have been generated to study its functions. In Inka2 -/- mice, cortical pyramidal neurons showed decreased dendritic spine density and aberrant morphology, along with marked activation/phosphorylation of downstream molecules of the Pak4 signal cascade like LIMK and Cofilin, indicating Inka2's role in dendritic spine development [1]. In smooth muscle cells (SMCs), Inka2 -/- SMCs exhibited accelerated cell migration ability with Cofilin activation, suggesting its role in SMC motility [2].

In conclusion, Inka2 is a critical mediator for actin reorganization in processes like dendritic spine development and SMC motility. The use of Inka2 CKO mouse models has been instrumental in revealing its role in these biological processes, contributing to our understanding of neural development and smooth muscle-related functions.

References:

1. Yamada, Seiya, Mizukoshi, Tomoya, Tokunaga, Akinori, Sakakibara, Shin-Ichi. 2022. Inka2, a novel Pak4 inhibitor, regulates actin dynamics in neuronal development. In PLoS genetics, 18, e1010438. doi:10.1371/journal.pgen.1010438. https://pubmed.ncbi.nlm.nih.gov/36301793/

2. Yamada, Seiya, Tokunaga, Akinori, Sakakibara, Shin-Ichi. 2022. Inka2 expression in smooth muscle cells and its involvement in cell migration. In Biochemical and biophysical research communications, 643, 55-60. doi:10.1016/j.bbrc.2022.12.068. https://pubmed.ncbi.nlm.nih.gov/36586159/

3. Liu, Yu-Yu, Tanikawa, Chizu, Ueda, Koji, Matsuda, Koichi. 2019. INKA2, a novel p53 target that interacts with the serine/threonine kinase PAK4. In International journal of oncology, 54, 1907-1920. doi:10.3892/ijo.2019.4786. https://pubmed.ncbi.nlm.nih.gov/31081062/

4. Iwasaki, Yumi, Yumoto, Takahito, Sakakibara, Shin-Ichi. 2015. Expression profiles of inka2 in the murine nervous system. In Gene expression patterns : GEP, 19, 83-97. doi:10.1016/j.gep.2015.08.002. https://pubmed.ncbi.nlm.nih.gov/26292052/

5. Akiyama, Hiroki, Iwasaki, Yumi, Yamada, Seiya, Kamiguchi, Hiroyuki, Sakakibara, Shin-Ichi. 2020. Control of cell migration by the novel protein phosphatase-2A interacting protein inka2. In Cell and tissue research, 380, 527-537. doi:10.1007/s00441-020-03169-x. https://pubmed.ncbi.nlm.nih.gov/31975032/