Year: 2014
Type: article
Abstract: Surface expression of voltage-gated Ca 2+ (Cav) channels is important for their function in calcium homeostasis in the physiology of excitable cells, but whether or not and how the α1 pore-forming subunits of Cav channels are trafficked to plasma membrane in the absence of the known Cav auxiliary subunits, β and α2δ, remains mysterious. Here we showed that 14-3-3 proteins promoted functional surface expression of the Cav2.2 α1B channel in transfected tsA-201 cells in the absence of any known Cav auxiliary subunit. Both the surface to total ratio of the expressed α1B protein and the current density of voltage step-evoked Ba 2+ current were markedly suppressed by the coexpression of a 14-3-3 antagonist construct, pSCM138, but not its inactive control, pSCM174, as determined by immunofluorescence assay and whole cell voltage clamp recording, respectively. By contrast, coexpression with 14-3-3τ significantly enhanced the surface expression and current density of the Cav2.2 α1B channel. Importantly, we found that between the two previously identified 14-3-3 binding regions at the α1B C terminus, only the proximal region (amino acids 1706–1940), closer to the end of the last transmembrane domain, was retained by the endoplasmic reticulum and facilitated by 14-3-3 to traffic to plasma membrane. Additionally, we showed that the 14-3-3/Cav β subunit coregulated the surface expression of Cav2.2 channels in transfected tsA-201 cells and neurons. Altogether, our findings reveal a previously unidentified regulatory function of 14-3-3 proteins in promoting the surface expression of Cav2.2 α1B channels. Background: The mechanism and dynamics of Cav channels trafficking remains mysterious. Results: 14-3-3τ promotes Cav2.2 trafficking independent of Cav auxiliary subunits. Conclusion: 14-3-3τ enhances Cav2.2 trafficking by masking the ER retention signal at its proximal C-terminal region. Significance: Uncovering the regulation of Cav2.2 trafficking may contribute to understanding the Cav2.2 surface expression and functional control under physiological and pathophysiological conditions.
Source: Journal of Biological Chemistry
Authors: Feng Liu, Qin Zhou, Jie Zhou, Hao Sun, Yan Wang, Xiuqun Zou, Lingling Feng, Zhaoyuan Hou, Aiwu Zhou, Yi Zhou, Yong Li
Institutions: Shanghai Jiao Tong University, Florida State University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W2080960522