α-Synuclein is a Novel Microtubule Dynamase.
α-Synuclein is a Novel Microtubule Dynamase.
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DOI：
10.1038/srep33289
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发表时间：
2016-09-15
影响因子：
4.6
通讯作者：
Cappelletti G
中科院分区：
文献类型：
--
作者：
Cartelli D;Aliverti A;Barbiroli A;Santambrogio C;Ragg EM;Casagrande FV;Cantele F;Beltramone S;Marangon J;De Gregorio C;Pandini V;Emanuele M;Chieregatti E;Pieraccini S;Holmqvist S;Bubacco L;Roybon L;Pezzoli G;Grandori R;Arnal I;Cappelletti G
α-突触核蛋白是一种与帕金森病相关的突触前蛋白，当游离在细胞质中时是非结构化的，当与囊泡结合时采用α螺旋构象。经过几十年的深入研究，α-突触核蛋白的生理学仍然很难弄清楚，因为它与多个伙伴相互作用，并参与了一系列神经元功能。在这里，我们研究了α-突触核蛋白和微管之间明显被忽视的相互作用，这可能会影响突触功能。为了确定这些作用的机制，我们研究了纯化的α-突触核蛋白和微管蛋白之间的相互作用。我们证明α-突触核蛋白与微管和微管蛋白α2β2四聚体结合;后者的相互作用诱导α-突触核蛋白多肽中螺旋片段的形成。这种结构变化似乎使α-Synuclein能够促进微管成核，并提高微管生长速率和突变频率，无论是在体外还是在细胞中。我们还发现，帕金森病相关的α-突触核蛋白变体不经历微管蛋白诱导的折叠，并导致微管蛋白聚集而不是聚合。我们的数据使我们能够提出α-突触核蛋白作为一种新的，可折叠的，微管动力酶，它通过与微管蛋白的结合及其对微管成核和动力学的调节作用来影响微管组织。
α-Synuclein is a presynaptic protein associated to Parkinson’s disease, which is unstructured when free in the cytoplasm and adopts α helical conformation when bound to vesicles. After decades of intense studies, α-Synuclein physiology is still difficult to clear up due to its interaction with multiple partners and its involvement in a pletora of neuronal functions. Here, we looked at the remarkably neglected interplay between α-Synuclein and microtubules, which potentially impacts on synaptic functionality. In order to identify the mechanisms underlying these actions, we investigated the interaction between purified α-Synuclein and tubulin. We demonstrated that α-Synuclein binds to microtubules and tubulin α2β2 tetramer; the latter interaction inducing the formation of helical segment(s) in the α-Synuclein polypeptide. This structural change seems to enable α-Synuclein to promote microtubule nucleation and to enhance microtubule growth rate and catastrophe frequency, both in vitro and in cell. We also showed that Parkinson’s disease-linked α-Synuclein variants do not undergo tubulin-induced folding and cause tubulin aggregation rather than polymerization. Our data enable us to propose α-Synuclein as a novel, foldable, microtubule-dynamase, which influences microtubule organisation through its binding to tubulin and its regulating effects on microtubule nucleation and dynamics.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4.8
作者：
Esteves, A. Raquel;Arduino, Daniela M.;Cardoso, Sandra M.
通讯作者：
Cardoso, Sandra M.
影响因子：
4.8
作者：
Ackmann, M;Wiech, H;Mandelkow, E
通讯作者：
Mandelkow, E
影响因子：
4.8
作者：
Honnappa, S;Cutting, B;Steinmetz, MO
通讯作者：
Steinmetz, MO
DOI：
10.1016/s0006-291x(71)80225-5
发表时间：
1971-01-01
影响因子：
3.1
作者：
CHEN, YH;YANG, JT
通讯作者：
YANG, JT