Journal Article

Retrograde regulation of synaptic vesicle endocytosis and recycling

Buchanan, JoAnn, Smith, Stephen J, Micheva, Kristina D, Holz, Ronald W

2003

Overview

Sustained release of neurotransmitter depends upon the recycling of synaptic vesicles. Until now, it has been assumed that vesicle recycling is regulated by signals from the presynaptic bouton alone, but results from rat hippocampal neurons reported here indicate that this need not be the case. Fluorescence imaging and pharmacological analysis show that a nitric oxide (NO) signal generated postsynaptically can regulate endocytosis and at least one later step in synaptic vesicle recycling. The proposed retrograde pathway involves an NMDA receptor (NMDAR)-dependent postsynaptic production of NO, diffusion of NO to a presynaptic site, and a cGMP-dependent increase in presynaptic phosphatidylinositol 4,5-biphosphate (PIP2). These results indicate that the regulation of synaptic vesicle recycling may integrate a much broader range of neural activity signals than previously recognized, including postsynaptic depolarization and the activation of NMDARs at both immediate and nearby postsynaptic active zones.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: Animal Genetics and Genomics / Animals / Behavioral Sciences / Biological Techniques / Biomedical and Life Sciences / Biomedicine / Cells, Cultured / Cyclic GMP - metabolism / Endocytosis / Endocytosis - physiology / Hippocampus - metabolism / Hippocampus - ultrastructure / Neurobiology / Neurosciences / Nitric oxide / Nitric Oxide - metabolism / Phosphatidylinositol 4,5-Diphosphate - metabolism / Physiological aspects / Rats / Receptors, N-Methyl-D-Aspartate - metabolism / Signal Transduction - physiology / Synapses / Synaptic vesicles / Synaptic Vesicles - metabolism / Synaptic Vesicles - ultrastructure