ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Rho-kinase accelerates synaptic vesicle endocytosis by linking cyclic GMP-dependent protein kinase activity to phosphatidylinositol-4,5-bisphosphate synthesis.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 32 citations in OpenAlex.
- Distinct Effects of Nonselective Rho-Kinase Inhibitor Fasudil and Selective Rho-Kinase 2 Inhibitor KD025 on Serotonin and Dopamine Release in the Nucleus Accumbens of Mice.Neuropsychopharmacology reports · 2026Article
- Anoxia-induced hippocampal LTP is regeneratively produced by glutamate and nitric oxide from the neuro-glial-endothelial axis.iScience · 2024Article
- Nanoscale Phosphoinositide Distribution on Cell Membranes of Mouse Cerebellar Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
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- Regulation of Presynaptic Calcium Channels.Advances in neurobiology · 2023Article
- The electrophysiologic properties of gonadotropin-releasing hormone neurons.Journal of neuroendocrinology · 2022Review
- Nitric oxide resets kisspeptin-excited GnRH neurons via PIP2 replenishment.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Article
- Presynaptic calcium channels: specialized control of synaptic neurotransmitter release.Nature reviews. Neuroscience · 2020Review
- Rho signaling research: history, current status and future directions.FEBS letters · 2018Review
- Activation of RHO-1 in cholinergic motor neurons competes with dopamine signalling to control locomotion.PloS one · 2018Article
- Wild-Type Monomeric α-Synuclein Can Impair Vesicle Endocytosis and Synaptic Fidelity via Tubulin Polymerization at the Calyx of Held.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Human Rho Guanine Nucleotide Exchange Factor 11 (ARHGEF11) Regulates Dendritic Morphogenesis.International journal of molecular sciences · 2016Article
- The calyx of Held in the auditory system: Structure, function, and development.Hearing research · 2016Review
- Cholesterol regulates multiple forms of vesicle endocytosis at a mammalian central synapse.Journal of neurochemistry · 2015Article
- Strength and precision of neurotransmission at mammalian presynaptic terminals.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2015Review
- The regulation of synaptic vesicle recycling by cGMP-dependent protein kinase type II in cerebellar granule cells under strong and sustained stimulation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Phosphoinositide metabolism links cGMP-dependent protein kinase G to essential Ca²⁺ signals at key decision points in the life cycle of malaria parasites.PLoS biology · 2014Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rho-kinase plays diverse roles in cell motility. During neuronal development, Rho-kinase is involved in neuronal migration, and in neurite outgrowth and retraction. Rho-kinase remains highly expressed in mature neurons, but its physiological roles are poorly understood. Here we report that Rho-kinase plays a key role in the synaptic vesicle recycling system in presynaptic terminals. Vesicles consumed by excessive exocytosis are replenished by accelerating vesicle endocytosis via a retrograde feedback mechanism involving nitric oxide released from postsynaptic cells. This homeostatic control system involves presynaptic cyclic GMP-dependent protein kinase (PKG) and a plasma membrane phospholipid, phosphatidylinositol-4,5-bisphophate (PIP2). We found that application of a Rho-kinase inhibitor, a PKG inhibitor or both, reduced the PIP2 content in Wistar rat brainstem synaptosomes to a similar extent. Likewise, application of the Rho-kinase inhibitor into the calyx of Held presynaptic terminal slowed vesicle endocytosis to the same degree as did application of the PKG inhibitor. This endocytic slowing effect of the Rho-kinase inhibitor was canceled by coapplication of PIP2 into the terminal. By contrast, a RhoA activator increased the PIP2 content and reversed the effect of the PKG inhibitor in brainstem synaptosomes. The RhoA activator, when loaded into calyceal terminals, also rescued the endocytic slowing effect of the PKG inhibitor. Furthermore, intraterminal loading of anti-PIP2 antibody slowed vesicle endocytosis and blocked the rescuing effect of the RhoA activator. We conclude that Rho-kinase links presynaptic PKG activity to PIP2 synthesis, thereby controlling the homeostatic balance of vesicle exocytosis and endocytosis in nerve terminals.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.