Cpne6, also known as Copine VI, is a member of the copines family, which are calcium-dependent phospholipids-binding proteins [1]. It is almost exclusively expressed in the brain and is involved in several biological processes. While its exact functions were initially unclear, studies suggest it may play a role in synaptic plasticity-related pathways, which are crucial for learning, memory, and normal neural function [2].

In a Cpne6 knockout mouse model, there was a deficiency in hippocampal long-term potentiation (LTP), a cellular process required for learning and memory. Hippocampal neurons from these knockouts lacked spine structural plasticity. This indicates that Cpne6 is essential for translating initial calcium signals into changes in spine structure, a process necessary for learning and memory. Specifically, Cpne6 functions by binding, activating, and recruiting the Rho GTPase Rac1 to cell membranes [2]. In addition, in patients with refractory epilepsy and a chronic pilocarpine-induced epileptic rat model, the expression of Cpne6 was found to increase remarkably. Double immunofluorescence labeling showed that Cpne6 protein is mainly expressed in neurons [1]. Also, in temporal lobe epilepsy, the interaction of adenylate kinase 5 (AK5) with Cpne6 increased [3].

In conclusion, Cpne6 is crucial for spine structural plasticity and learning and memory processes, as demonstrated by knockout mouse models. Its abnormal expression is associated with epilepsy, highlighting its importance in understanding the pathophysiology of this neurological disorder. These findings from model-based research provide insights into the role of Cpne6 in normal neural function and disease conditions.

References:

1. Zhu, Binglin, Zha, Jingsi, Long, Yan, Chen, Guojun, Wang, Xuefeng. 2015. Increased expression of copine VI in patients with refractory epilepsy and a rat model. In Journal of the neurological sciences, 360, 30-6. doi:10.1016/j.jns.2015.11.041. https://pubmed.ncbi.nlm.nih.gov/26723968/

2. Reinhard, Judith R, Kriz, Alexander, Galic, Milos, Vogt, Kaspar E, Ruegg, Markus A. 2016. The calcium sensor Copine-6 regulates spine structural plasticity and learning and memory. In Nature communications, 7, 11613. doi:10.1038/ncomms11613. https://pubmed.ncbi.nlm.nih.gov/27194588/

3. Lai, Yujie, Hu, Xiaotong, Chen, Guojun, Wang, Xuefeng, Zhu, Binglin. 2016. Down-regulation of adenylate kinase 5 in temporal lobe epilepsy patients and rat model. In Journal of the neurological sciences, 366, 20-26. doi:10.1016/j.jns.2016.04.037. https://pubmed.ncbi.nlm.nih.gov/27288770/