Trafficking of Presynaptic PMCA Signaling Complexes in Mouse Photoreceptors Requires Cav1.4 α1 Subunits
The pore-forming Cav1.4 α1 subunit of the L-type Ca2+ channel plays a critical role in voltage-dependent Ca2+ influx and transmitter release at mammalian photoreceptor and bipolar synapses. Here we ask whether loss of Cav1.4 protein in the nob2 (“no b-wave”) Cacna1f mutation affects expression and localization of Ca2+ extrusion machinery at retinal ribbon synapses. Analysis of PMCA1, PMCA2, and pan-PMCA immunoreactivity in nob2 retinas showed pronounced mislocalization of presynaptic proteins in rod photoreceptors but not in bipolar neurons. PMCA1 transporters were displaced into juxtanuclear pockets across the outer nuclear layer (ONL) whereas little change was observed in localization of the high affinity Ca2+ extruder PMCA2. Our results therefore implicate Cav1.4 subunits in proper development and trafficking of signaling complexes to the photoreceptor synapse.
KeywordsCalcium extrusion Nob2 Photoreceptor Cacna1f Voltage-operated PMCA PMCA1 Ribbon synapse Retina
The work was supported by The National Institutes of Health (EY13870, P30EY014800, EY 12497), The Foundation Fighting Blindness, and the Moran TIGER award. The research was also supported by an unrestricted award from Research to Prevent Blindness to the Moran Eye Institute at the University of Utah.
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