Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
Electrophysiology Laboratory of the Multidisciplinary Institute of Cell Biology (Argentine Research Council CONICET, Scientific Research Commission of the Buenos Aires Province and National University of La Plata, La Plata, Buenos Aires, Argentina.
Channels (Austin). 2023 Dec;17(1):2230776. doi: 10.1080/19336950.2023.2230776.
Missense mutations in the human secretary carrier-associated membrane protein 5 (SCAMP5) cause a variety of neurological disorders including neurodevelopmental delay, epilepsy, and Parkinson's disease. We recently documented the importance of SCAMP2 in the regulation of T-type calcium channel expression in the plasma membrane. Here, we show that similar to SCAMP2, the co-expression of SCAMP5 in tsA-201 cells expressing recombinant Ca3.1, Ca3.2, and Ca3.3 channels nearly abolished whole-cell T-type currents. Recording of intramembrane charge movements revealed that SCAMP5-induced inhibition of T-type currents is primarily caused by the reduced expression of functional channels in the plasma membrane. Moreover, we show that SCAMP5-mediated downregulation of Ca3.2 channels is essentially preserved with disease-causing SCAMP5 R91W and G180W mutations. Hence, this study extends our previous findings with SCAMP2 and indicates that SCAMP5 also contributes to repressing the expression of T-type channels in the plasma membrane.
人分泌载体相关膜蛋白 5（SCAMP5）中的错义突变可导致多种神经紊乱，包括神经发育迟缓、癫痫和帕金森病。我们最近证明了 SCAMP2 在调节细胞膜上 T 型钙通道表达中的重要性。在这里，我们表明类似于 SCAMP2，在表达重组 Ca3.1、Ca3.2 和 Ca3.3 通道的 tsA-201 细胞中共表达 SCAMP5 几乎完全消除了全细胞 T 型电流。膜内电荷运动的记录表明，SCAMP5 诱导的 T 型电流抑制主要是由于功能性通道在质膜中的表达减少所致。此外，我们表明，SCAMP5 介导的 Ca3.2 通道下调与致病的 SCAMP5 R91W 和 G180W 突变基本保持不变。因此，本研究扩展了我们之前关于 SCAMP2 的发现，并表明 SCAMP5 也有助于抑制 T 型通道在质膜中的表达。
