Turku Bioscience, University of Turku and Åbo Akademi University, Tykistokatu 6, 20500 Turku, Finland.
University of Helsinki, Neuroscience Center, 00014 Helsinki, Finland.
Cells. 2020 Feb 14;9(2):440. doi: 10.3390/cells9020440.
The protein kinase JNK1 exhibits high activity in the developing brain, where it regulates dendrite morphology through the phosphorylation of cytoskeletal regulatory proteins. JNK1 also phosphorylates dendritic spine proteins, and mice display a long-term depression deficit. Whether JNK1 or other JNKs regulate spine morphology is thus of interest. Here, we characterize dendritic spine morphology in hippocampus of mice lacking using Lucifer yellow labelling. We find that mushroom spines decrease and thin spines increase in apical dendrites of CA3 pyramidal neurons with no spine changes in basal dendrites or in CA1. Consistent with this spine deficit, mice display impaired acquisition learning in the Morris water maze. In hippocampal cultures, we show that cytosolic but not nuclear JNK, regulates spine morphology and expression of phosphomimicry variants of JNK substrates doublecortin (DCX) or myristoylated alanine-rich C kinase substrate-like protein-1 (MARCKSL1), rescue mushroom, thin, and stubby spines differentially. These data suggest that physiologically active JNK controls the equilibrium between mushroom, thin, and stubby spines via phosphorylation of distinct substrates.
蛋白激酶 JNK1 在发育中的大脑中表现出高活性，通过磷酸化细胞骨架调节蛋白来调节树突形态。JNK1 还磷酸化树突棘蛋白，而 JNK1 缺失的小鼠表现出长期抑郁缺陷。因此，JNK1 或其他 JNK 是否调节棘突形态引起了人们的兴趣。在这里，我们使用 Lucifer yellow 标记来描述缺乏 JNK1 的小鼠海马中的树突棘形态。我们发现 CA3 锥体神经元的树突棘形态发生改变，蘑菇状棘突减少，而细棘突增加，基底树突或 CA1 无棘突变化。与这种棘突缺陷一致，JNK1 缺失的小鼠在 Morris 水迷宫中的获得性学习能力受损。在海马培养物中，我们表明细胞质而非核 JNK 调节棘突形态，并且 JNK 底物的磷酸模拟变体双皮质素 (DCX) 或肉豆蔻酰化丙氨酸丰富 C 激酶底物样蛋白 1 (MARCKSL1) 的表达，通过磷酸化不同的底物来拯救蘑菇状、细状和短粗状棘突。这些数据表明，生理活性 JNK 通过磷酸化不同的底物来控制蘑菇状、细状和短粗状棘突之间的平衡。
