![]() From the ER membrane, proteins are then trafficked to the plasma membrane via the Golgi network and trafficking endosomes ( Figure 2). ![]() Ĭa V channel subunits are synthesized by ER-bound ribosomes and inserted into the ER membrane while being synthesized. β subunits can bind Ca Vα 1 subunits in the endoplasmic reticulum (ER) prior to processing in the Golgi, and the resulting Ca Vα 1-β subunit complex is often found to be localized at the plasma membrane. However, it has also been reported that β subunits most likely interact with other regions of Ca Vα 1 subunits. The ABP binds to a region called the AID domain in the I–II loop of the Ca Vα 1 subunit, which contains several key residues that modulate β subunit binding. The effects of β subunits on HVA channels are mediated by the GK domain, through a region termed the α Interaction Domain (AID) Binding Pocket (ABP). The GK and SH3 domains are highly conserved across the different β subunits, and are connected by a variable HOOK domain. All β subunits consist of five distinct structural regions: the N-terminus, the src homology 3 (SH3) domain, the HOOK domain, the GK domain, and the C-terminus. However, palmitoylation of the β 2a subunit takes place post-translationally at its N-terminus and results in the targeting of the subunit to the plasma membrane. There are four different types of β subunits (encoded by four genes) and they are largely cytoplasmic. Schematic representation of the structure of Ca V channelsĪuxilliary β subunits are crucial for the regulation of HVA channel activity through modulation of their biophysical properties and the control of their membrane trafficking. Conversely, LVA channels only require a Ca Vα 1 subunit to be functional. These subunits include the pore forming Ca Vα 1 subunit and auxiliary α 2δ and β subunits, and in some cases a γ subunit. All HVA channels contain multiple subunits which assemble to form a functional channel complex ( Figure 1). Ca V channels are activated by membrane depolarization and they can be classified into two major categories: high-voltage-activated channels (HVAs), consisting of L-type (Ca V1.1, 1.2, 1.3 and 1.4), P/Q-type (Ca V2.1), N-type (Ca V2.2), and R-type (Ca V2.3) channels, and low-voltage-activated channels (LVAs), which encompass the T-type channels (Ca V3.1, Ca V3.2, Ca V3.3). In neurons, voltage-gated Ca 2+ (Ca V) channels are expressed in most plasma membrane compartments and they are involved in regulating cell excitability, gene transcription and synaptic transmission. Calcium (Ca 2+) channels mediate numerous important physiological processes, and are abundant in many types of cells.
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