Abstract
Several studies have shown the importance of calcium channels in the development and/or maturation of synapses. The Ca(V)1.4(α(1F)) knockout mouse is a unique model to study the role of calcium channels in photoreceptor synapse formation. It features abnormal ribbon synapses and aberrant cone morphology. We investigated the expression and targeting of several key elements of ribbon synapses and analyzed the cone morphology in the Ca(V)1.4(α(1F)) knockout retina. Our data demonstrate that most abnormalities occur after eye opening. Indeed, scaffolding proteins such as Bassoon and RIM2 are properly targeted at first, but their expression and localization are not maintained in adulthood. This indicates that either calcium or the Ca(V)1.4 channel, or both are necessary for the maintenance of their normal expression and distribution in photoreceptors. Other proteins, such as Veli3 and PSD-95, also display abnormal expression in rods prior to eye opening. Conversely, vesicle related proteins appear normal. Our data demonstrate that the Ca(V)1.4 channel is important for maintaining scaffolding proteins in the ribbon synapse but less vital for proteins related to vesicular release. This study also confirms that in adult retinae, cones show developmental features such as sprouting and synaptogenesis. Overall we present evidence that in the absence of the Ca(V)1.4 channel, photoreceptor synapses remain immature and are unable to stabilize.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adaptor Proteins, Signal Transducing / genetics
-
Adaptor Proteins, Signal Transducing / metabolism
-
Aging / genetics*
-
Animals
-
Animals, Newborn
-
Calcium Channels / genetics
-
Calcium Channels / metabolism*
-
Calcium Channels, L-Type
-
Disks Large Homolog 4 Protein
-
Gene Expression Profiling
-
Gene Expression Regulation, Developmental*
-
Guanylate Kinases / genetics
-
Guanylate Kinases / metabolism
-
Membrane Proteins / genetics
-
Membrane Proteins / metabolism
-
Mice
-
Mice, Knockout
-
Microscopy, Electron, Transmission
-
Nerve Tissue Proteins / genetics
-
Nerve Tissue Proteins / metabolism
-
Retinal Cone Photoreceptor Cells / metabolism*
-
Retinal Cone Photoreceptor Cells / ultrastructure
-
Retinal Rod Photoreceptor Cells / metabolism*
-
Retinal Rod Photoreceptor Cells / ultrastructure
-
Synapses / genetics
-
Synapses / metabolism*
-
Synapses / ultrastructure
-
rab3 GTP-Binding Proteins / genetics
-
rab3 GTP-Binding Proteins / metabolism
Substances
-
Adaptor Proteins, Signal Transducing
-
Bsn protein, mouse
-
Cacna1f protein, mouse
-
Calcium Channels
-
Calcium Channels, L-Type
-
Disks Large Homolog 4 Protein
-
Dlg4 protein, mouse
-
Lin7c protein, mouse
-
Membrane Proteins
-
Nerve Tissue Proteins
-
Guanylate Kinases
-
Rim2 protein, mouse
-
rab3 GTP-Binding Proteins
Grants and funding
This work was supported by a grant of the Behrens-Weise-Stiftung. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.