U1216, INSERM, Grenoble, F-38000, France.
Grenoble Institute of Neuroscience, Université Grenoble Alpes, Grenoble, France.
Eur J Neurosci. 2017 Dec;46(11):2754-2767. doi: 10.1111/ejn.13766. Epub 2017 Nov 22.
MAP6 proteins were first described as microtubule-stabilizing agents, whose properties were thought to be essential for neuronal development and maintenance of complex neuronal networks. However, deletion of all MAP6 isoforms in MAP6 KO mice does not lead to dramatic morphological aberrations of the brain but rather to alterations in multiple neurotransmissions and severe behavioural impairments. A search for protein partners of MAP6 proteins identified Tctex1 - a dynein light chain with multiple non-microtubule-related functions. The involvement of Tctex1 in calcium signalling led to investigate it in MAP6 KO neurons. In this study, we show that functional Ca 2.2/N-type calcium channels are deficient in MAP6 KO neurons, due to improper location. We also show that MAP6 proteins interact directly with both Tctex1 and the C-terminus of Ca 2.2/N-type calcium channels. A balance of these two interactions seems to be crucial for MAP6 to modulate calcium signalling in neurons.
MAP6 蛋白最初被描述为微管稳定剂，其特性被认为对神经元发育和复杂神经网络的维持至关重要。然而，在 MAP6 KO 小鼠中敲除所有 MAP6 同工型并不会导致大脑出现明显的形态异常，而是导致多种神经递质传递和严重的行为障碍的改变。对 MAP6 蛋白的蛋白伴侣的搜索确定了 Tctex1——一种具有多种非微管相关功能的动力蛋白轻链。Tctex1 参与钙信号转导，导致在 MAP6 KO 神经元中对其进行研究。在这项研究中，我们表明，由于位置不当，功能性 Ca 2.2/N 型钙通道在 MAP6 KO 神经元中缺失。我们还表明，MAP6 蛋白直接与 Tctex1 和 Ca 2.2/N 型钙通道的 C 末端相互作用。这两种相互作用的平衡似乎对 MAP6 调节神经元中的钙信号至关重要。
