TMEM16A is associated with voltage-gated calcium channels in mouse retina and its function is disrupted upon mutation of the auxiliary α2δ4 subunit.

摘要: Photoreceptors rely upon highly specialized synapses to efficiently transmit signals multiple postsynaptic targets. Calcium influx in the presynaptic terminal is mediated by voltage-gated calcium channels (VGCC). This event triggers neurotransmitter release, but also gates calcium-activated chloride (TMEM), which turn regulate VGCC activity. In order investigate relationship between and TMEM channels, we analyzed retina of wild type (WT) Cacna2d4 mutant mice, auxiliary α2δ4 subunit carries a nonsense mutation, disrupting normal channel function. Synaptic terminals photoreceptors are disarranged synaptic proteins as well TMEM16A lose their characteristic localization. parallel, currents impaired rods, despite unaltered protein levels. Co-immunoprecipitation revealed interaction retina. Heterologous expression these tsA-201 cells showed that associates with CaV1.4 subunit, association persists subunit. Collectively, our experiments show α1 VGCC. Close proximity allows optimal function photoreceptor under physiological conditions, makes susceptible changes occurring channels.