MODULATION OF VOLTAGE-GATED CALCIUM CHANNEL BY A SYNAPTIC PROTEIN AND GANGLIOSIDE

Voltage-gated calcium channels play a vital role in triggering the vesicle release in presynaptic terminals. We have identified several molecules in modulating the calcium channel functions. One of our focus is snapin from presynaptic complex, and the other is gangliosides and anti-gangliosides antibodies. We found that snapin could increase current density of voltage-gated calcium channels in an isoform- and splice-variant-selective manner. Notably, the CaV2.1 and CaV2.2 channels are mutually exclusively spliced to produce either CaV2.1[EFa] or CaV2.1[EFb], and CaV2.2[EFa] or CaV2.2[EFb] respectively. Snapin selectively increased the current density of CaV2.1[EFb] and CaV2.2[EFa], but not CaV2.1[EFa] and CaV2.2[EFb]. Moreover, snapin preferentially modulated CaV1.3 channel by interacting with the I-II loop region but not on the other calcium channel of CaV1 families. In addition, voltage-gated calcium channels were modulated by anti-ganglioside antibodies. The antibodies against ganglioside are found in patient sera of Guillain-Barre syndrome, though the underlying pathogenesis is not clear yet. We discovered that anti-ganglioside antibodies modulated voltage sensing of the Ca2+ channel. The opening threshold of voltage-gated calcium channel are either reduced or increased by anti-GM1 and anti-GQ1b antibodies respectively. These interactions between voltage-gated calcium channel and anti-ganglioside antibodies are dependent on the auxiliary a2d subunit of calcium channel.

Author dc:creator

• LIN QINGSHU

• voltage-gated calcium channel, alternative splicing, snapin, ganglioside