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- Title
Rab3A Mediates Vesicle Delivery at Photoreceptor Ribbon Synapses.
- Authors
Tian, Miao; Shan Xu, C.; Montpetit, Rachel; Kramer, Richard H.
- Abstract
Rab3A is a synaptic vesicle-associated protein found throughout the nervous system, but its precise function is unknown. Genetic knock-out studies show that Rab3A is not necessary for vesicular release or replenishment at conventional synapses in the brain. Here we explore the function of Rab3A at ribbon synapses in the retina of the tiger salamander (Ambystoma tigrinum). Fluorescently labeled Rab3A, delivered into rods and cones through a patch pipette, binds to and dissociates from synaptic ribbons. Experiments using nonphosphorylatable GDP analogs and a GTPase-deficient Rab3A mutant indicate that ribbon binding and dissociation are governed by a GTP hydrolysis cycle. Paired recordings from presynaptic photoreceptors and postsynaptic OFF-bipolar cells show that the Rab3A mutant blocks synaptic release in an activity-dependent manner, with more frequent stimulation leading to more rapid block. The frequency dependence of block by exogenous Rab3A suggests that it acts competitively with synaptic vesicles to interfere with their resupply to release sites. Together, these findings suggest a crucial role of Rab3A in delivering vesicles to Ca2+-dependent release sites at ribbon synapses.
- Subjects
PHOTORECEPTORS; SYNAPSES; BRAIN function localization; GUANOSINE triphosphatase; CALCIUM ions; HYDROLYSIS
- Publication
Journal of Neuroscience, 2012, Vol 32, Issue 20, p6931
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0265-12.2012