Micellar nanocomplexes for biomagnetic delivery of intracellular proteins to dictate axon formation during neuronal development.
Micellar nanocomplexes for biomagnetic delivery of intracellular proteins to dictate axon formation during neuronal development.
复制标题
DOI：
10.1016/j.biomaterials.2016.09.035
复制
发表时间：
2017-01
期刊：
影响因子：
14
通讯作者：
Shelly, Maya
中科院分区：
文献类型：
--
作者：
Suarato, Giulia;Lee, Seong-Il;Li, Weiyi;Rao, Sneha;Khan, Tanvir;Meng, Yizhi;Shelly, Maya
关键词：
在哺乳动物胚胎发育期间，神经元分裂以产生轴突和树突的不同细胞隔室，其在形式和功能上固有地不同，为神经系统中的定向信号提供基础。极化是由特定蛋白质的活动在时空上分离到神经元的离散区域而产生的，从而决定轴突与树突的命运。我们的目标是操纵轴突形成的关键细胞内蛋白质功能的定向亚细胞定位。在这里，我们报告的关键步骤，发展的纳米技术，局部亚细胞内的激酶，LKB 1，轴突形成的关键调节器的引入和保留。这种纳米技术将在培养和体内开发啮齿动物神经元中空间操纵LKB 1连接的生物磁性纳米复合物（LKB 1-NCs）。我们创建了一个超分子组装LKB 1快速神经元摄取和延长细胞质稳定性。LKB 1-NC保留了激酶活性和磷酸化的下游靶标。成功地将NCs递送到培养的胚胎海马神经元中，并且在细胞质中稳定2天，这足够用于轴突形成。重要的是，LKB 1-NCs促进了这些神经元中轴突的形成，代表了细胞内蛋白质功能在支配中枢发育事件中的充分性的独特概念证明。最后，我们在子宫内建立了NC向活大鼠胚胎脑皮质祖细胞的递送。我们的纳米技术为细胞内蛋白质活性的空间操纵提供了一个可行的平台，以决定神经元发育过程中的中心事件。
During mammalian embryonic development, neurons polarize to create distinct cellular compartments of axon and dendrite that inherently differ in form and function, providing the foundation for directional signaling in the nervous system. Polarization results from spatiotemporal segregation of specific proteins’ activities to discrete regions of the neuron to dictate axonal vs. dendritic fate. We aim to manipulate axon formation by directed subcellular localization of crucial intracellular protein function. Here we report critical steps toward the development of a nanotechnology for localized subcellular introduction and retention of an intracellular kinase, LKB1, crucial regulator of axon formation. This nanotechnology will spatially manipulate LKB1-linked biomagnetic nanocomplexes (LKB1-NCs) in developing rodent neurons in culture and in vivo. We created a supramolecular assembly for LKB1 rapid neuronal uptake and prolonged cytoplasmic stability. LKB1-NCs retained kinase activity and phosphorylated downstream targets. NCs were successfully delivered to cultured embryonic hippocampal neurons, and were stable in the cytoplasm for 2 days, sufficient time for axon formation. Importantly, LKB1-NCs promoted axon formation in these neurons, representing unique proof of concept for the sufficiency of intracellular protein function in dictating a central developmental event. Lastly, we established NC delivery into cortical progenitors in live rat embryonic brain in utero. Our nanotechnology provides a viable platform for spatial manipulation of intracellular protein-activity, to dictate central events during neuronal development.
登录
查看更多内容
影响因子：
13.9
作者：
Barnes AP;Polleux F
通讯作者：
Polleux F
影响因子：
38.3
作者：
Etoc, F.;Lisse, D.;Dahan, M.
通讯作者：
Dahan, M.
影响因子：
3.3
作者：
Biernat, J;Wu, YZ;Mandelkow, EM
通讯作者：
Mandelkow, EM
影响因子：
9.2
作者：
Fivaz, Marc;Bandara, Samuel;Meyer, Tobias
通讯作者：
Meyer, Tobias
DOI：
10.1073/pnas.0509955103
发表时间：
2006-05-30
影响因子：
11.1
作者：
Chen, Y. M.;Wang, Q. J.;Luo, Z. G.
通讯作者：
Luo, Z. G.