T-type calcium channels perform crucial physiological roles across a wide spectrum of tissues, spanning both neuronal and non-neuronal system. For instance, they serve as pivotal regulators of neuronal excitability, contribute to cardiac pacemaking, and mediate the secretion of hormones. These functions significantly hinge upon the intricate interplay of T-type channels with interacting proteins that modulate their expression and function at the plasma membrane. In this review, we offer a panoramic exploration of the current knowledge surrounding these T-type channel interactors, and spotlight certain aspects of their potential for drug-based therapeutic intervention.

• Keywords
• Calcium channels, Channelosome, Ion channels, T-type channels,
• MeSH
• Calcium Channel Blockers MeSH
• Neurons metabolism   MeSH
• Calcium * metabolism   MeSH
• Calcium Channels, T-Type * metabolism   MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Calcium Channel Blockers MeSH
• Calcium * MeSH
• Calcium Channels, T-Type * MeSH

Low-voltage-activated T-type calcium channels are important contributors to nervous system function. Post-translational modification of these channels has emerged as an important mechanism to control channel activity. Previous studies have documented the importance of asparagine (N)-linked glycosylation and identified several asparagine residues within the canonical consensus sequence N-X-S/T that is essential for the expression and function of Cav3.2 channels. Here, we explored the functional role of non-canonical N-glycosylation motifs in the conformation N-X-C based on site directed mutagenesis. Using a combination of electrophysiological recordings and surface biotinylation assays, we show that asparagines N345 and N1780 located in the motifs NVC and NPC, respectively, are essential for the expression of the human Cav3.2 channel in the plasma membrane. Therefore, these newly identified asparagine residues within non-canonical motifs add to those previously reported in canonical sites and suggest that N-glycosylation of Cav3.2 may also occur at non-canonical motifs to control expression of the channel in the plasma membrane. It is also the first study to report the functional importance of non-canonical N-glycosylation motifs in an ion channel.

• Keywords
• Asparagine-linked glycosylation, Calcium channel, N-glycosylation, Non-canonical glycosylation, T-type channel, Trafficking, cav3.2 Channel,
• MeSH
• Amino Acid Motifs MeSH
• Asparagine metabolism   MeSH
• Glycosylation MeSH
• Humans MeSH
• Calcium Channels, T-Type chemistry   metabolism   MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Asparagine MeSH
• CACNA1H protein, human MeSH Browser
• Calcium Channels, T-Type MeSH