title: Neurofilament subunits are integral components of synapses and modulate neurotransmission and behavior in vivo.
abstract: Synaptic roles for neurofilament (NF) proteins have rarely been considered. Here, we establish all four NF subunits as integral resident proteins of synapses. Compared with the population in axons, NF subunits isolated from synapses have distinctive stoichiometry and phosphorylation state, and respond differently to perturbations in vivo. Completely eliminating NF proteins from brain by genetically deleting three subunits (α-internexin, NFH and NFL) markedly depresses hippocampal long-term potentiation induction without detectably altering synapse morphology. Deletion of NFM in mice, but not the deletion of any other NF 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 NF subunits and establish their key role in neurotransmission in vivo, suggesting potential novel influences of NF proteins in psychiatric as well as neurological states.
authors: 1] Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, USA [2] Department of Psychiatry, New York University School of Medicine, New York, NY, USA.
authors: A
authors: A
authors: Yuan
authors: 1] Department of Psychiatry, New York University School of Medicine, New York, NY, USA [2] Neurochemistry Division, Nathan Kline Institute, Orangeburg, NY, USA.
authors: H
authors: H
authors: Sershen
authors: 1] Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, USA [2] Department of Psychiatry, New York University School of Medicine, New York, NY, USA.
authors: Veeranna
authors: 1] Analytical Psychopharmacology Division, Nathan Kline Institute, Orangeburg, NY, USA [2] Department of Psychiatry, College of Physicians & Surgeons, Columbia University, New York, NY, USA.
authors: B S
authors: BS
authors: Basavarajappa
authors: 1] Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, USA [2] Department of Psychiatry, New York University School of Medicine, New York, NY, USA.
authors: A
authors: A
authors: Kumar
authors: Neurochemistry Division, Nathan Kline Institute, Orangeburg, NY, USA.
authors: A
authors: A
authors: Hashim
authors: Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, USA.
authors: M
authors: M
authors: Berg
authors: 1] Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, USA [2] Department of Psychiatry, New York University School of Medicine, New York, NY, USA.
authors: J-H
authors: JH
authors: Lee
authors: Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, USA.
authors: Y
authors: Y
authors: Sato
authors: 1] Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, USA [2] Department of Psychiatry, New York University School of Medicine, New York, NY, USA.
authors: M V
authors: MV
authors: Rao
authors: Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, USA.
authors: P S
authors: PS
authors: Mohan
authors: Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, USA.
authors: V
authors: V
authors: Dyakin
authors: Centre de Recherche du Centre Hospitalier de l'Université Laval, Département d'anatomie et physiologie de l'Université Laval, Québec, QC, Canada.
authors: J-P
authors: JP
authors: Julien
authors: Department of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors: V M-Y
authors: VM
authors: Lee
authors: 1] Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, USA [2] Department of Psychiatry, New York University School of Medicine, New York, NY, USA [3] Department of Cell Biology, New York University School of Medicine, New York, NY, USA.
authors: R A
authors: RA
authors: Nixon
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D003042:Cocaine / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000502:physiology; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D018765:Dopamine Uptake Inhibitors; C583261:Drd1 protein, mouse; D016900:Neurofilament Proteins; D017447:Receptors, Dopamine D1; D003042:Cocaine