Myosin IIb activity and phosphorylation status determines dendritic spine and post-synaptic density morphology.
Myosin IIb activity and phosphorylation status determines dendritic spine and post-synaptic density morphology.
复制标题
DOI：
10.1371/journal.pone.0024149
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Horwitz AR
中科院分区：
文献类型：
--
作者：
Hodges JL;Newell-Litwa K;Asmussen H;Vicente-Manzanares M;Horwitz AR
海马神经元中的树突棘从丝状伪足样前体成熟为具有扩大的突触后密度（PSD）的蘑菇状，并作为兴奋性神经传递的主要突触后位点，而兴奋性神经传递是学习和记忆的基础。利用肌球蛋白II调节突变体、抑制剂和基因敲低技术，我们发现非肌肉肌球蛋白IIB（MIIB）的活性决定了树突棘在何处形成，以及它们是作为丝状伪足样树突棘前体持续存在还是成熟为蘑菇状。MIIB还决定了PSD的大小、形态以及在树突棘中的位置。MIIB的局部失活会导致从树突干形成丝状伪足样树突棘突起。然而，Rho激酶对调节轻链上的苏氨酸18和丝氨酸19残基进行双磷酸化是树突棘成熟所必需的。抑制MIIB活性或调节轻链（RLC）的单磷酸化模拟突变体即使在存在N -甲基 - D -天冬氨酸（NMDA）受体激活的情况下也同样会阻止成熟。表达一种肌动蛋白交联的、非收缩性突变体MIIB R709C表明，成熟为蘑菇状需要收缩活性。MIIB的缺失还会导致PSD形态拉长，不再局限于树突棘尖端；而MIIB活性的增加，特别是通过RLC - T18、S19双磷酸化，会增加PSD面积。这些观察结果支持一种模型，即肌球蛋白II失活形成丝状伪足样突起，只有当NMDA受体激活增加RLC双磷酸化以刺激MIIB收缩性时，这些突起才会成熟，从而形成具有扩大PSD的蘑菇状树突棘。
Dendritic spines in hippocampal neurons mature from a filopodia-like precursor into a mushroom-shape with an enlarged post-synaptic density (PSD) and serve as the primary post-synaptic location of the excitatory neurotransmission that underlies learning and memory. Using myosin II regulatory mutants, inhibitors, and knockdowns, we show that non-muscle myosin IIB (MIIB) activity determines where spines form and whether they persist as filopodia-like spine precursors or mature into a mushroom-shape. MIIB also determines PSD size, morphology, and placement in the spine. Local inactivation of MIIB leads to the formation of filopodia-like spine protrusions from the dendritic shaft. However, di-phosphorylation of the regulatory light chain on residues Thr18 and Ser19 by Rho kinase is required for spine maturation. Inhibition of MIIB activity or a mono-phosphomimetic mutant of RLC similarly prevented maturation even in the presence of NMDA receptor activation. Expression of an actin cross-linking, non-contractile mutant, MIIB R709C, showed that maturation into a mushroom-shape requires contractile activity. Loss of MIIB also leads to an elongated PSD morphology that is no longer restricted to the spine tip; whereas increased MIIB activity, specifically through RLC-T18, S19 di-phosphorylation, increases PSD area. These observations support a model whereby myosin II inactivation forms filopodia-like protrusions that only mature once NMDA receptor activation increases RLC di-phosphorylation to stimulate MIIB contractility, resulting in mushroom-shaped spines with an enlarged PSD.
登录
查看更多内容
影响因子：
16.2
作者：
Frost, Nicholas A.;Shroff, Hari;Kong, Huihui;Betzig, Eric;Blanpied, Thomas A.
通讯作者：
Blanpied, Thomas A.
DOI：
10.1083/jcb.200204153
发表时间：
2002-11-25
期刊：
The Journal of cell biology
影响因子：
--
作者：
Galbraith CG;Yamada KM;Sheetz MP
通讯作者：
Sheetz MP
影响因子：
56.9
作者：
Kimura, K;Ito, M;Kaibuchi, K
通讯作者：
Kaibuchi, K
影响因子：
21.3
作者：
Choi, Colin K.;Vicente-Manzanares, Miguel;Zareno, Jessica;Whitmore, Leanna A.;Mogilner, Alex;Horwitz, Alan Rick
通讯作者：
Horwitz, Alan Rick
DOI：
10.1083/jcb.200809046
发表时间：
2009-04-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hotulainen P;Llano O;Smirnov S;Tanhuanpää K;Faix J;Rivera C;Lappalainen P
通讯作者：
Lappalainen P