Molecular bioelectricity: how endogenous voltage potentials control cell behavior and instruct pattern regulation in vivo.
Molecular bioelectricity: how endogenous voltage potentials control cell behavior and instruct pattern regulation in vivo.
复制标题
DOI：
10.1091/mbc.e13-12-0708
复制
发表时间：
2014-12-01
影响因子：
3.3
通讯作者：
Levin M
中科院分区：
文献类型：
--
作者：
Levin M
除了生物化学梯度和转录网络之外，细胞行为还受到源自离子通道和泵活性的内源性生物电信号的调节，这些信号在多种细胞类型中起作用。由静息电位变化介导的指导性信号控制干细胞、祖细胞和体细胞的增殖、分化、细胞形状和凋亡。然而，重要的是，细胞不仅受到自身VEGF-I的调节，还受到邻近细胞VEGF-I的调节，通过称为间隙连接的电突触形成网络。非神经躯体组织中VEGFR 1分布的时空变化调节模式形成，并作为触发肢体再生、诱导眼睛形成、设置全身解剖轴极性和编排颅面模式的信号。用于跟踪和功能改变体内VEGF-C梯度的新工具已经确定了生物电信号的新作用，并揭示了VEGF-C变化被转导到下游基因表达级联的分子途径。因为通道和间隙连接是后向门控的，所以生物电网络具有其自身的特征动力学，其不减少通道表达的分子分析（尽管它们在功能上与转录网络耦合）。最近的数据提供了一个令人兴奋的机会来破解生物电密码，并学会在器官水平上编程细胞活动，而不仅仅是细胞类型。了解图案信息如何在生物电网络中编码，这可能需要计算神经科学的概念，将对胚胎发生，再生，癌症和合成生物工程产生变革性的影响。
In addition to biochemical gradients and transcriptional networks, cell behavior is regulated by endogenous bioelectrical cues originating in the activity of ion channels and pumps, operating in a wide variety of cell types. Instructive signals mediated by changes in resting potential control proliferation, differentiation, cell shape, and apoptosis of stem, progenitor, and somatic cells. Of importance, however, cells are regulated not only by their own Vmem but also by the Vmem of their neighbors, forming networks via electrical synapses known as gap junctions. Spatiotemporal changes in Vmem distribution among nonneural somatic tissues regulate pattern formation and serve as signals that trigger limb regeneration, induce eye formation, set polarity of whole-body anatomical axes, and orchestrate craniofacial patterning. New tools for tracking and functionally altering Vmem gradients in vivo have identified novel roles for bioelectrical signaling and revealed the molecular pathways by which Vmem changes are transduced into cascades of downstream gene expression. Because channels and gap junctions are gated posttranslationally, bioelectrical networks have their own characteristic dynamics that do not reduce to molecular profiling of channel expression (although they couple functionally to transcriptional networks). The recent data provide an exciting opportunity to crack the bioelectric code, and learn to program cellular activity at the level of organs, not only cell types. The understanding of how patterning information is encoded in bioelectrical networks, which may require concepts from computational neuroscience, will have transformative implications for embryogenesis, regeneration, cancer, and synthetic bioengineering.