Yuan A, Sershen H, Basavarajappa B S, Kumar A, Hashim A, Berg M, Lee J-H, Sato Y, Rao M V, Mohan P S, Dyakin V, Julien J-P, Lee V M-Y, Nixon R A
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.
1] Department of Psychiatry, New York University School of Medicine, New York, NY, USA [2] Neurochemistry Division, Nathan Kline Institute, Orangeburg, NY, USA.
Mol Psychiatry. 2015 Aug;20(8):986-94. doi: 10.1038/mp.2015.45. Epub 2015 Apr 14.
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.
神经丝（NF）蛋白的突触作用很少被考虑。在这里，我们确定所有四种NF亚基都是突触的组成性驻留蛋白。与轴突中的群体相比，从突触中分离出的NF亚基具有独特的化学计量和磷酸化状态，并且在体内对扰动的反应不同。通过基因敲除三个亚基（α-中间丝蛋白、NFH和NFL）完全从大脑中消除NF蛋白，显著抑制海马体长期增强诱导，而未检测到突触形态的改变。在小鼠中敲除NFM，但不敲除任何其他NF亚基，会增强多巴胺D1受体介导的对可卡因的运动反应，同时将突触后D1受体从内体重新分布到质膜，这与NFM在D1受体循环中的特定调节作用一致。这些结果确定了突触NF亚基的一个独特群体，并确立了它们在体内神经传递中的关键作用，表明NF蛋白在精神状态以及神经状态中可能具有新的影响。
