Cell signalling crosstalk in development

发育中的细胞信号串扰

• 批准号: 183825-2009
• 负责人: Kelly, Gregory
• 金额: $ 2.33万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2011
• 资助国家: 加拿大
• 起止时间: 2011-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=476433
• 关键词: Cell; signalling; crosstalk; development

Communication between cells is no different than that between individuals over a phone, where ideally one speaks and the other listens. Carrying a conversation relies on active participants that trade places, taking turns speaking and listening. With cell phones, information travels from the mobile device to a number of towers in a network, finding the quickest route to the appropriate receiver. Given the number of calls made in any one network and at any one time, there is a chance your call may disrupt someone else's in what is called undesirable crosstalk. Cell-cell communication is comparable and cells have multiple networks each a signaling pathway composed of numerous protein components that receive and pass on information in the form of molecular signals to and from the nucleus. Unlike cell phone communication, cells have networks that are interconnected and allow for desirable crosstalk, linking many pathways and providing a mechanism that finely tunes the original signal and the cell's response depending on the conditions. What starts out as beneficial to a cell, however, can turn disastrous when undesirable crosstalk upsets the balance and the original signal gets misinterpreted. This is the case when one signaling pathway accepts the wrong signal into the network, or accepts the right one, but at the wrong time. This also happens when a signaling pathway is flooded with crosstalk from multiple pathways. This mis-information weakens the integrity of the entire signaling network. For a cell, the end result is the breakdown in the normal circuitry, which has dire consequences as there is now uncontrollable "chatter" and no way to "hand-off" the appropriate signal to the next player. My major objective is to understand how signaling pathways decipher and regulate the crosstalk converging on them, allowing for the correct flow of molecular information to occur while quenching undesirable signaling. Elucidating the mechanisms by which cells use crosstalk to modulate signaling pathways during embryonic development is of great importance as atypical, unnecessary and often surplus crosstalk is correlated later to disease conditions including, but not limited to cancer, kidney disease, osteoporosis and Schizophrenia.

细胞之间的交流与个人之间通过电话进行的交流没有什么不同，理想的情况是一个人说话，另一个人倾听。进行对话依赖于积极的参与者，他们交换位置，轮流说和听。使用手机，信息从移动设备传输到网络中的多个塔，找到到达适当接收器的最快路径。考虑到在任何一个网络中和在任何一个时间进行的呼叫数量，您的呼叫有可能在所谓的不良串扰中干扰其他人的呼叫。细胞与细胞之间的通讯具有可比性，细胞有多个网络，每个网络都是由许多蛋白质成分组成的信号通路，以分子信号的形式向细胞核收发信息，并从细胞核传递信息。与手机通信不同的是，手机的网络是相互连接的，允许理想的串扰，连接许多路径，并提供一种机制，根据条件微调原始信号和手机的反应。然而，当不受欢迎的串扰扰乱了平衡，原始信号被曲解时，最初对细胞有益的东西可能会变成灾难性的。这种情况下，一个信令路径接受错误的信号进入网络，或接受正确的信号，但在错误的时间。当一条信号通路被来自多条通路的串扰淹没时，也会发生这种情况。这种错误信息削弱了整个信令网络的完整性。对于电池来说，最终结果是正常电路的故障，这会产生可怕的后果，因为现在有无法控制的“颤动”，没有办法将适当的信号“传递”给下一个玩家。我的主要目标是了解信号通路如何破译和调节汇聚在它们身上的串扰，从而在消除不良信号的同时允许正确的分子信息流发生。阐明细胞在胚胎发育过程中利用串扰来调节信号通路的机制非常重要，因为非典型的、不必要的、经常是多余的串扰后来与疾病相关，包括但不限于癌症、肾脏疾病、骨质疏松症和精神分裂症。