Secretory carrier-associated membrane protein 5 regulates cell-surface targeting of T-type calcium channels.
Emilio Román MustafáKonstantin WeißNorbert WeissPublished in: Channels (Austin, Tex.) (2023)
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 Ca v 3.1, Ca v 3.2, and Ca v 3.3 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 Ca v 3.2 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.
Keyphrases
- poor prognosis
- cell surface
- endothelial cells
- binding protein
- single cell
- induced apoptosis
- cell proliferation
- protein kinase
- mesenchymal stem cells
- cell therapy
- oxidative stress
- drug delivery
- autism spectrum disorder
- cancer therapy
- bone marrow
- intellectual disability
- diabetic rats
- induced pluripotent stem cells
- cerebral ischemia
- endoplasmic reticulum stress
- stress induced