Lateral Mobility of Presynaptic L-Type Calcium Channels at Photoreceptor Ribbon Synapses

Abstract

At most synapses, presynaptic Ca2+ channels are positioned near vesicle release sites, and increasing this distance reduces synaptic strength. We examined the lateral membrane mobility of presynaptic L-type Ca2+ channels at photoreceptor ribbon synapses of the tiger salamander (Ambystoma tigrinum) retina. Movements of individual Ca2+ channels were tracked by coupling quantum dots to an antibody against the extracellular α2δ4 Ca2+ channel subunit. α2δ4 antibodies labeled photoreceptor terminals and co-localized with antibodies to synaptic vesicle protein SV2 and Ca2+ channel CaV1.4 α1 subunits. The results show that Ca2+ channels are dynamic and move within a confined region beneath the synaptic ribbon. The size of this confinement area is regulated by actin and membrane cholesterol. Fusion of nearby synaptic vesicles caused jumps in Ca2+ channel position, propelling them towards the outer edge of the confinement domain. Channels rebounded rapidly towards the center. Thus, although CaV channels are mobile, molecular scaffolds confine them beneath the ribbon to maintain neurotransmission even at high release rates.

Actin-dependent rapid recruitment of reluctant synaptic vesicles into a fast-releasing vesicle pool

“…It has been found recently that at photoreceptor ribbon synapses presynaptic Ca 2+ channels are mobile in a confinement domain, probably an AZ (26). Furthermore, actin disruption enlarges such domains and abolishes their movements associated with stimulation (26).…”

Congenital stationary night blindness: An analysis and update of genotype–phenotype correlations and pathogenic mechanisms

“…Similarly, the a2d4 (CACNA2D4) protein is most likely the a2d-subunit in photoreceptors (Fig. 14), as animals and patients have a similar icCSNB and cone/cone-rod/rod-cone dystrophy phenotype (Wycisk et al, 2006a(Wycisk et al, , 2006b and the protein localizes in photoreceptor synapses in the OPL (Mercer et al, 2011). The Ca 2þ influx through Cav1.4 channels triggers the continuous release of glutamate from the photoreceptor synapse in the dark to the ONbipolar dendrites which express mainly the high-affinity, sixth subtype metabotropic glutamate receptor (GRM6 also called mGluR6) (see 5.3 Molecules important for glutamate-induced signalling from the photoreceptors to ON-bipolar cells (GRM6, GPR179, NYX, TRPM1, LRIT3); horizontal cells as well as OFFbipolar cells employ ionotropic glutamate receptors (for review (Wassle, 2004)).…”

Clarin-1 gene transfer rescues auditory synaptopathy in model of Usher syndrome

“…Could the disruption of F-actin be responsible for the spatial disorganization of the Ca V 1.3 Ca 2+ channels? It has been suggested that a direct association between Ca V β 2 and F-actin promotes the directional transport of Ca 2+ channels to the plasma membrane of cardiomyocytes (34), and, at the ribbon synapse of salamander photoreceptors, the confinement of Ca 2+ channels beneath the ribbon is regulated by actin and membrane cholesterol (35). The disruption of F-actin with latrunculin-A in WT IHCs has been shown to disrupt the spatial distribution of Ca V 1.3 Ca 2+ channels (23) in a manner similar to that observed here, in the active zones of IHCs lacking clarin-1 from the 2 types of mutant mice.…”