The HOOK region of voltage-gated Ca2+ channel β subunits senses and transmits PIP2 signals to the gate

Abstract

Voltage-gated Ca2+ channels contain β subunits that regulate channel gating. Park et al. conduct a comprehensive analysis of the role of the β subunit HOOK region and show that its B domain is important for PIP2 regulation of channel gating and that its A domain modulates this effect.

The HOOK region of β subunits controls gating of voltage-gated Ca2+ channels by electrostatically interacting with plasma membrane

“…We recently found that 2 hydrophobic Phe residues in the B domain are needed for decreasing the inactivation kinetics and PIP 2 sensitivity of the Ca V 2.2 channels. 24 Consistently, the Phe-mutated form (b2cPhe Ala ) also slightly decrease the current density of the channels (Fig. 3C and D).…”

“…24 Here, we examined whether the HOOK region of the b subunit also affects the voltage-dependent inactivation (VDI) and voltage-dependent activation (VDA) of the Ca V channels. Fig.…”

“…Since charged amino acids of the HOOK region are mainly important in regulating inactivation kinetics and PIP 2 sensitivity of Ca V 2.2 channels, 24 we examined whether the charged amino acids of the HOOK region also influence the current density of the Ca V 2.2 channels. As shown in Fig.…”

“…24 We then examined whether the HOOK region also influences the PIP 2 sensitivity and inactivation kinetics of L-type Ca V 1.3 channels. As shown in Fig.…”

“…24 The HOOK region can be further divided into 3 domains on the basis of amino acid composition: S (polyserine), A (polyacidic), and B (polybasic). Acidic residues within the A domain are needed for the increase of channel inhibition by PIP 2 depletion and the fast inactivation of Ca V 2.2 current like cytosolic b subunits, while basic amino acids within the B region are needed for the decrease in PIP 2 sensitivity and the slow inactivation like membrane-localized b subunits.…”