A key function for microtubule-associated-protein 6 in activity-dependent stabilisation of actin filaments in dendritic spines
A key function for microtubule-associated-protein 6 in activity-dependent stabilisation of actin filaments in dendritic spines
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微管相关蛋白 6 在树突棘肌动蛋白丝活性依赖性稳定中的关键功能
DOI：
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发表时间：
2018
影响因子：
16.6
通讯作者：
A. Andrieux
中科院分区：
文献类型：
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作者：
Leticia Peris;M. Bisbal;J. Martinez;Y. Saoudi;Julie Jonckheere;Marta Rolland;Muriel Sébastien;J. Brocard;E. Denarier;C. Bosc;Christophe Guérin;S. Gory;J. Deloulme;Fabien Lanté;I. Arnal;A. Buisson;Y. Goldberg;L. Blanchoin;C. Delphin;A. Andrieux
新出现的证据表明微管相关蛋白（MAPs）与突触功能有关；特别是，缺乏MAP6的小鼠在可塑性和认知方面表现出显著的缺陷。MAP6与可塑性机制的联系尚不清楚。在这里，我们讨论了这种蛋白质在树突棘中的可能作用。我们发现，在缺乏MAP6的皮质和海马神经元中，成熟脊柱的维护受损，可以通过表达MAP6序列的一段称为Mc模块的片段来恢复。Mc模块直接结合肌动蛋白丝并介导树突棘中f -肌动蛋白的活性依赖稳定，这是突触可塑性的关键事件。在体外，Mc模块增强肌动蛋白丝成核，促进稳定、高度有序的丝束的形成。活动诱导的MAP6磷酸化可能控制其向脊柱细胞骨架的转移。这些结果为MAP6在认知中的作用提供了分子解释，揭示了细胞骨架功能障碍、突触损伤和神经精神疾病之间的联系。微管相关蛋白6 （MAP6）被认为是突触可塑性和认知的重要因素，可能通过与微管的相互作用。在这里，作者发现MAP6通过与不同的细胞骨架元素肌动蛋白的关联，对扩大的突触的稳定至关重要。
Emerging evidence indicates that microtubule-associated proteins (MAPs) are implicated in synaptic function; in particular, mice deficient for MAP6 exhibit striking deficits in plasticity and cognition. How MAP6 connects to plasticity mechanisms is unclear. Here, we address the possible role of this protein in dendritic spines. We find that in MAP6-deficient cortical and hippocampal neurons, maintenance of mature spines is impaired, and can be restored by expressing a stretch of the MAP6 sequence called Mc modules. Mc modules directly bind actin filaments and mediate activity-dependent stabilisation of F-actin in dendritic spines, a key event of synaptic plasticity. In vitro, Mc modules enhance actin filament nucleation and promote the formation of stable, highly ordered filament bundles. Activity-induced phosphorylation of MAP6 likely controls its transfer to the spine cytoskeleton. These results provide a molecular explanation for the role of MAP6 in cognition, enlightening the connection between cytoskeletal dysfunction, synaptic impairment and neuropsychiatric illnesses. Microtubule-associated protein 6 (MAP6) is known to be important for synaptic plasticity and cognition, supposedly via interaction with microtubules. Here, the authors found that MAP6 is crucial for the stabilisation of enlarged synapses through its association with a different cytoskeletal element, actin.
DOI：
10.1083/jcb.200512058
发表时间：
2006-09-11
期刊：
The Journal of cell biology
影响因子：
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作者：
Peris L;Thery M;Fauré J;Saoudi Y;Lafanechère L;Chilton JK;Gordon-Weeks P;Galjart N;Bornens M;Wordeman L;Wehland J;Andrieux A;Job D
通讯作者：
Job D
影响因子：
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作者：
Penzes, Peter;Rafalovich, Igor
通讯作者：
Rafalovich, Igor