Department of Neuroscience, Centro de Biología Molecular Severo Ochoa CSIC/UAM, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
J Biol Chem. 2011 Nov 25;286(47):40638-48. doi: 10.1074/jbc.M111.271320. Epub 2011 Oct 7.
Microtubule-associated protein 1B (MAP1B) is prominently expressed during early stages of neuronal development, and it has been implicated in axonal growth and guidance. MAP1B expression is also found in the adult brain in areas of significant synaptic plasticity. Here, we demonstrate that MAP1B is present in dendritic spines, and we describe a decrease in the density of mature dendritic spines in neurons of MAP1B-deficient mice that was accompanied by an increase in the number of immature filopodia-like protrusions. Although these neurons exhibited normal passive membrane properties and action potential firing, AMPA receptor-mediated synaptic currents were significantly diminished. Moreover, we observed a significant decrease in Rac1 activity and an increase in RhoA activity in the post-synaptic densities of adult MAP1B(+/-) mice when compared with wild type controls. MAP1B(+/-) fractions also exhibited a decrease in phosphorylated cofilin. Taken together, these results indicate a new and important role for MAP1B in the formation and maturation of dendritic spines, possibly through the regulation of the actin cytoskeleton. This activity of MAP1B could contribute to the regulation of synaptic activity and plasticity in the adult brain.
微管相关蛋白 1B(MAP1B)在神经元发育的早期阶段表达明显,它与轴突生长和导向有关。MAP1B 的表达也在成年大脑中具有重要突触可塑性的区域中发现。在这里,我们证明 MAP1B 存在于树突棘中,并且我们描述了 MAP1B 缺陷型小鼠中成熟树突棘密度的降低,伴随着不成熟的丝状伪足样突起数量的增加。尽管这些神经元表现出正常的被动膜特性和动作电位发放,但 AMPA 受体介导的突触电流显著减少。此外,与野生型对照相比,我们在成年 MAP1B(+/-)小鼠的突触后密度中观察到 Rac1 活性的显著降低和 RhoA 活性的增加。MAP1B(+/-)分数也表现出磷酸化丝切蛋白的减少。总之,这些结果表明 MAP1B 在树突棘的形成和成熟中具有新的和重要的作用,可能通过调节肌动蛋白细胞骨架。MAP1B 的这种活性可能有助于调节成年大脑中的突触活动和可塑性。