Neurofilament Subunits are Integral Components of Synapses and Modulate Neurotransmission and Behavior In Vivo
| Autor: | V M-Y Lee, J Julien, Audrey Hashim, J.E. Lee, Ralph A. Nixon, Panaiyur S. Mohan, Martin J. Berg, Mala V. Rao, Aidong Yuan, Asok Kumar, Veeranna, Henry Sershen, Victor V. Dyakin, Yutaka Sato, Balapal S. Basavarajappa |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Neurofilament
Endosome Protein subunit Population Long-Term Potentiation D1 receptor cocaine Biology Neurotransmission Motor Activity Synaptic Transmission Article Synapse Cellular and Molecular Neuroscience Dopamine Uptake Inhibitors Postsynaptic potential Neurofilament Proteins Animals education Molecular Biology Mice Knockout education.field_of_study synaptic plasticity Receptors Dopamine D1 Brain Long-term potentiation Axons Psychiatry and Mental health Synapses LTP stimulant drug Neuroscience |
| Zdroj: | Molecular psychiatry |
| ISSN: | 1476-5578 1359-4184 |
| Popis: | Synaptic roles for neurofilament proteins have rarely been considered. Here, we establish all four neurofilament subunits as integral resident proteins of synapses. Compared to the population in axons, neurofilament subunits isolated from synapses have distinctive stoichiometry and phosphorylation state, and respond differently to perturbations in vivo. Completely eliminating neurofilament proteins from brain by genetically deleting three subunits (α-internexin, NFH and NFL) markedly depresses hippocampal LTP induction without detectably altering synapse morphology. Deletion of NFM in mice, but not the deletion of any other neurofilament subunit, amplifies dopamine D1-receptor-mediated motor responses to cocaine while redistributing postsynaptic D1-receptors from endosomes to plasma membrane, consistent with a specific modulatory role of NFM in D1-receptor recycling. These results identify a distinct pool of synaptic neurofilament subunits and establish their key role in neurotransmission in vivo, suggesting potential novel influences of neurofilament proteins in psychiatric as well as neurological states. |
| Databáze: | OpenAIRE |
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