The role of ectodomain shedding in neurodevelopment

胞外域脱落在神经发育中的作用

• 批准号: RGPIN-2017-05593
• 负责人: Fournier, Alyson
• 金额: $ 2.04万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629255
• 关键词: role; ectodomain; shedding; neurodevelopment

During development cells in the nervous system wire together to form connections that regulate a multitude of simple and complex behaviors including sensory processing, motor control and cognition. Proper wiring requires nerve cells or neurons to extend processes through a complex environment to correct targets and to establish stable connections with other neurons are target tissues through contacts called synapses. Mutations in proteins required for synapse formation have been linked to neurodevelopmental disorders such as autism spectrum disorders. Further, normal remodeling of synapses is fundamental to our ability to learn and remember. Neurons express a host of receptor molecules on their cell surface that permit them to respond to environmental cues to form, stabilize and remodel synaptic connection. The ability of the cell to change its response to the extracellular environment is influenced by the ability of cells to shed cell surface proteins. Shedding of cell surface molecules can desensitize neurons to their environment and can also release bioactive fragments into the neuronal environment. Protein shedding is controlled by a family of proteins calls metalloproteinases that can desensitize neurons to cues in the environment by rapidly remodeling the repertoire of surface proteins. In this way neurons can dynamically regulate their response to the environment in space and time. We are studying the important roles that metalloproteinases play in spatial and temporal regulation of synapse formation. These studies will shed light on the fundamental science underlying synapse formation and remodeling, key processes underlying proper neuronal development and memory formation.

在发育过程中，神经系统中的细胞连接在一起，形成连接，调节包括感觉处理、运动控制和认知在内的大量简单和复杂的行为。正确的连接需要神经细胞或神经元通过复杂的环境延长过程，以纠正目标，并通过称为突触的接触与其他神经元建立稳定的连接。突触形成所需蛋白质的突变与神经发育障碍有关，如自闭症谱系障碍。此外，突触的正常重塑是我们学习和记忆能力的基础。神经元在其细胞表面表达一系列受体分子，使它们能够对环境线索做出反应，以形成、稳定和重塑突触连接。细胞改变其对细胞外环境的反应的能力受到细胞脱落细胞表面蛋白的能力的影响。细胞表面分子的脱落可以使神经元对环境不敏感，也可以将生物活性碎片释放到神经元环境中。蛋白质的脱落是由一种名为金属蛋白酶的蛋白质家族控制的，它可以通过快速重塑表面蛋白质的谱系，使神经元对环境中的暗示不敏感。通过这种方式，神经元可以在空间和时间上动态地调节它们对环境的反应。我们正在研究金属蛋白酶在突触形成的空间和时间调节中所起的重要作用。这些研究将阐明突触形成和重塑的基础科学，以及正常神经元发育和记忆形成的关键过程。