β-COP Suppresses the Surface Expression of the TREK2

Abstract

K2P channels, also known as two-pore domain K+ channels, play a crucial role in maintaining the cell membrane potential and contributing to potassium homeostasis due to their leaky nature. The TREK, or tandem of pore domains in a weak inward rectifying K+ channel (TWIK)-related K+ channel, subfamily within the K2P family consists of mechanical channels regulated by various stimuli and binding proteins. Although TREK1 and TREK2 within the TREK subfamily share many similarities, β-COP, which was previously known to bind to TREK1, exhibits a distinct binding pattern to other members of the TREK subfamily, including TREK2 and the TRAAK (TWIK-related acid-arachidonic activated K+ channel). In contrast to TREK1, β-COP binds to the C-terminus of TREK2 and reduces its cell surface expression but does not bind to TRAAK. Furthermore, β-COP cannot bind to TREK2 mutants with deletions or point mutations in the C-terminus and does not affect the surface expression of these TREK2 mutants. These results emphasize the unique role of β-COP in regulating the surface expression of the TREK family.

An Overview of the Mechanisms Involved in Neuralgia

“…Decreased expression of K2p1.1 leads to membrane depolarization and increased neuronal excitability, rendering them sensitive to mechanical and thermal stimuli. 70,71 In a study by Jia et al, it was found that systemic administration of paclitaxel resulted in a time-dependent reduction in K2p1.1 mRNA and protein expression in DRG neurons, leading to mechanical and thermal hypersensitivity in rats. Additionally, overexpression of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) in DRG improved the expression of K+ channel 1.1 (K(2p)1.1) and alleviated mechanical heterotopic pain as well as heat and cold pain on the affected side in rats.…”