Effects of Presynaptic Mutations on a Postsynaptic Cacna1s Calcium Channel Colocalized with mGluR6 at Mouse Photoreceptor Ribbon Synapses

Abstract

Presynaptic mutations leading to reduced photoreceptor-to-bipolar cell signaling are associated with disturbances in protein expression within postsynaptic dendrites. Moreover, detection of Cacna1s and Serca2 in ON-bipolar cell dendrites in wild-type animals suggests a putative role in regulation of postsynaptic Ca(2+) flux.

Characterization of Cav1.4 Complexes (α11.4, β2, and α2δ4) in HEK293T Cells and in the Retina

“…4). High magnification images showed anti-Ca v 1.4 ␣ 1 labeling of elongated and horseshoeshaped structures corresponding to the photoreceptor synaptic ribbon that arches around the postsynaptic terminals, as described previously (13,33). In these experiments, we also tested for the co-immunoprecipitation of CaBP4, a known Ca v 1.4-interacting protein (28,42).…”

Complex Regulation of Voltage-dependent Activation and Inactivation Properties of Retinal Voltage-gated Cav1.4 L-type Ca2+ Channels by Ca2+-binding Protein 4 (CaBP4)

“…This retinal disease is characterized by loss of neurotransmission from rods to second order bipolar cells, which is attributable to a loss of Cav1.4. These findings are corroborated by the analysis of a genetic mouse model deficient for the Cav1.4 ␣ 1 subunit (8,9). In addition, in the mouse, deletion of another component of the Cav1.4 channel complex, the auxiliary ␤ 2a subunit, also leads to CSNB2-like phenotype (10).…”

Deletion of the Presynaptic Scaffold CAST Reduces Active Zone Size in Rod Photoreceptors and Impairs Visual Processing

“…Sprouting of postsynaptic elements into the ONL with aberrant formation of synapses has been found in retinae of mouse mutants with impaired synaptic transmission (Haeseleer et al, 2004;Mansergh et al, 2005;Chang et al, 2006;Specht et al, 2007Specht et al, , 2009. Therefore, we investigated whether this was also the case in CAST Ϫ/Ϫ mice and could potentially contribute to the reduction of OPL width.…”

“…For vesicle densities, the number of vesicles directly attached to the ribbon were counted at each profile and divided by the ribbon profile length visible in the micrograph [ Specht et al, 2009); mouse anti-Cacna1s (mab1A; 1:5000 for ICC), rabbit anti-PKC␣ (1: 1000 for ICC; Sigma), rabbit anti-mGluR6 (1:100 for ICC; Neuromics), rabbit anti-Veli3 (1:1000 for ICC; Zymed), mouse anti-CtBP2/RIBEYE (1: 10,000 for ICC; 1:1000 for WB; BD Biosciences), guinea pig anti-Piccolo (1:8000 for ICC; kindly provided by E. Gundelfinger, Magdeburg, Germany), mouse anti-Bassoon (mab7f; 1:2500 for ICC; Stressgen), rabbit anti-Calbindin (1:1000 for ICC; Swant), anti-b-dystroglycan (1:500 for ICC; Novocastra), and rabbit anti-RIM2-Znfinger (1:500; Synaptic Systems).…”