AHNAK, also known as neuroblast differentiation-associated protein, is a large, ubiquitously expressed scaffolding phosphoprotein. It plays a crucial role in various biological processes. It is involved in mediating protein-protein interactions, enabling it to participate in multi-protein complexes. Key functions include calcium homeostasis (largely interacting with L-type voltage-gated calcium channel in excitable cells), immune regulation, cell architecture maintenance, and tumor suppression. It is also implicated in pathways like Wnt/β-catenin, TGF-β/Smad, and BMP2-mediated adipocyte differentiation [1,2,3,4,5].

In Ahnak knockout (KO) mouse models, several findings have been revealed. In liver regeneration, Ahnak KO mice showed faster initial liver weight-to-body weight ratio increase after 70% partial hepatectomy, as Ahnak enhances TGF-β signaling during postoperative liver regeneration, disrupting the cell cycle [4]. In adipocyte differentiation, adipocytes from Ahnak KO mice were smaller, and Ahnak knockdown in cell lines severely impaired adipocyte differentiation, suggesting Ahnak regulates adipogenesis through Smad1-dependent PPARγ expression [5].

In conclusion, AHNAK is essential for multiple biological processes such as calcium regulation, cell cycle control during liver regeneration, and adipocyte differentiation. The use of Ahnak KO mouse models has provided valuable insights into its role in these processes and related disease conditions like liver diseases and obesity-related disorders.

References:

1. Sundararaj, Srinivasan, Ravindran, Agin, Casarotto, Marco G. 2021. AHNAK: The quiet giant in calcium homeostasis. In Cell calcium, 96, 102403. doi:10.1016/j.ceca.2021.102403. https://pubmed.ncbi.nlm.nih.gov/33813182/

2. Davis, T A, Loos, B, Engelbrecht, A-M. 2014. AHNAK: the giant jack of all trades. In Cellular signalling, 26, 2683-93. doi:10.1016/j.cellsig.2014.08.017. https://pubmed.ncbi.nlm.nih.gov/25172424/

3. Cai, Yanlin, Hu, Yi, Yu, Furong, Sheng, Shunliang, Zhu, Jiayu. 2021. AHNAK suppresses ovarian cancer progression through the Wnt/β-catenin signaling pathway. In Aging, 13, 23579-23587. doi:10.18632/aging.203473. https://pubmed.ncbi.nlm.nih.gov/34689136/

4. Yang, Insook, Son, Yeri, Shin, Jae Hoon, Kim, Il Yong, Seong, Je Kyung. . Ahnak depletion accelerates liver regeneration by modulating the TGF-β/Smad signaling pathway. In BMB reports, 55, 401-406. doi:. https://pubmed.ncbi.nlm.nih.gov/35880432/

5. Shin, Sunmee, Seong, Je Kyung, Bae, Yun Soo. 2016. Ahnak stimulates BMP2-mediated adipocyte differentiation through Smad1 activation. In Obesity (Silver Spring, Md.), 24, 398-407. doi:10.1002/oby.21367. https://pubmed.ncbi.nlm.nih.gov/26813528/