A dual role for Cav1.4 Ca2+ channels in the molecular and structural organization of the rod photoreceptor synapse
Abstract
Synapses are fundamental information processing units that rely on voltage-gated Ca2+ (Cav) channels to trigger Ca2+-dependent neurotransmitter release. Cav channels also play Ca2+-independent roles in other biological contexts, but whether they do so in axon terminals is unknown. Here, we addressed this unknown with respect to the requirement for Cav1.4 L-type channels for the formation of rod photoreceptor synapses in the retina. Using a mouse strain expressing a non-conducting mutant form of Cav1.4, we report that the Cav1.4 protein, but not its Ca2+ conductance, is required for the molecular assembly of rod synapses; however, Cav1.4 Ca2+ signals are needed for the appropriate recruitment of postsynaptic partners. Our results support a model in which presynaptic Cav channels serve both as organizers of synaptic building blocks and as sources of Ca2+ ions in building the first synapse of the visual pathway and perhaps more broadly in the nervous system.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files
Article and author information
Author details
Funding
National Eye Institute (EY 026817)
- Amy Lee
McPherson Eye Research Institute
- Mrinalini Hoon
Research to Prevent Blindness
- Mrinalini Hoon
National Eye Institute (EY 029953)
- J Wesley Maddox
National Eye Institute (EY 026477)
- Brittany Williams
National Eye Institute (EY010843,EY012682)
- Nikolai Artemyev
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Teresa Giraldez, Universidad de La Laguna, Spain
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#7121262-025) of the University of Iowa. The protocol was approved by the Office of Institutional Animal Care and Use Committee of the University of Iowa (A3021-01).
Version history
- Received: August 17, 2020
- Accepted: September 9, 2020
- Accepted Manuscript published: September 17, 2020 (version 1)
- Version of Record published: October 15, 2020 (version 2)
Copyright
© 2020, Maddox et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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