Ca2+ sensor synaptotagmin-1 mediates exocytosis in mammalian photoreceptors
- University of Nebraska Medical Center, United States
Abstract
To encode light-dependent changes in membrane potential, rod and cone photoreceptors utilize synaptic ribbons to sustain continuous exocytosis while making rapid, fine adjustments to release rate. Release kinetics are shaped by vesicle delivery down ribbons and by properties of exocytotic Ca2+ sensors. We tested the role for synaptotagmin-1 (Syt1) in photoreceptor exocytosis by using novel mouse lines in which Syt1 was conditionally removed from rods or cones. Photoreceptors lacking Syt1 exhibited marked reductions in exocytosis as measured by electroretinography and single-cell recordings. Syt1 mediated all evoked release in cones, whereas rods appeared capable of some slow Syt1-independent release. Spontaneous release frequency was unchanged in cones but increased in rods lacking Syt1. Loss of Syt1 did not alter synaptic anatomy or reduce Ca2+ currents. These results suggest that Syt1 mediates both phasic and tonic release at photoreceptor synapses, revealing unexpected flexibility in the ability of Syt1 to regulate Ca2+-dependent synaptic transmission.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figure 9.
Article and author information
Author details
Justin J Grassmeyer
Channabasavaiah B Gurumurthy
Wallace B Thoreson
Funding
National Eye Institute (EY10542)
- Wallace B Thoreson
Research to Prevent Blindness (Senior Scientific Investigator)
- Wallace B Thoreson
National Eye Institute (EY28848)
- Justin J Grassmeyer
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal care and handling protocols were approved by the University of Nebraska Medical Center Institutional Animal Care and Use Committee (protocols 15-027-00 and 15-028-04).
Copyright
© 2019, Grassmeyer 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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Ca2+ sensor synaptotagmin-1 mediates exocytosis in mammalian photoreceptors
eLife 8:e45946.
https://doi.org/10.7554/eLife.45946
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