Abstract
T-type calcium channels are key contributors to neuronal physiology where they shape electrical activity of nerve cells and contribute to the release of neurotransmitters. Alteration of T-type channel expression has been causally linked to a number of pathological conditions including neuropathic pain and absence seizure activity. Although a number of signaling pathways regulating the activity of T-type calcium channels have been reported, the molecular machinery and signaling molecules controlling the trafficking and expression of the channel protein at the plasma membrane remain largely unknown. I will present some of the basic mechanisms recently identified controlling the physiological trafficking of T-type channels, and illustrate how metabolic defects or congenital mutations can disturb this trafficking machinery and eventually leading to disease conditions.
Publications
Proft J, Rzhepetskyy Y, Lazniewska J, Zhang FX, Snutch TP, Zamponi GW, Weiss N (2017) The Cacna1h mutation in the GAERS model of absence epilepsy enhances T-type Ca2+ currents by altering calnexin- dependent trafficking of Cav3.2 channels. Sci Reports 7:11513.
Weiss N, Zamponi GW (2017) Trafficking of neuronal calcium channels. Neuronal Signaling 1:1-16.
Lazniewska J, Rzhepetskyy Y, Zhang FX, Zamponi GW, Weiss N (2016) Cooperative roles of glucose and asparagine-linked glycosylation in T-type calcium channel expression. Pflügers Arch – Eur J Physiol 468:1837-1851.
Rzhepetskyy Y, Lazniewska J, Proft J, Campiglio M, Flucher B, Weiss N (2016) A Cav3.2/Stac1 molecular complex controls T-type channel expression at the plasma membrane. Channels (Austin) 10:346-354.
Weiss N, Black S, Bladen C, Chen L, Zamponi GW (2013) Surface expression and function of Cav3.2 T-type calcium channels is controlled by asparagine-linked glycosylation. Pflügers Arch – Eur J Physiol 465:1159-1170.
|
