精神分裂症易感基因失调结合蛋白控制突触稳态。
The schizophrenia susceptibility gene dysbindin controls synaptic homeostasis.
作者信息
Dickman Dion K, Davis Graeme W
机构信息
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA.
出版信息
Science. 2009 Nov 20;326(5956):1127-30. doi: 10.1126/science.1179685.
Abstract
The molecular mechanisms that achieve homeostatic stabilization of neural function remain largely unknown. To better understand how neural function is stabilized during development and throughout life, we used an electrophysiology-based forward genetic screen and assessed the function of more than 250 neuronally expressed genes for a role in the homeostatic modulation of synaptic transmission in Drosophila. This screen ruled out the involvement of numerous synaptic proteins and identified a critical function for dysbindin, a gene linked to schizophrenia in humans. We found that dysbindin is required presynaptically for the retrograde, homeostatic modulation of neurotransmission, and functions in a dose-dependent manner downstream or independently of calcium influx. Thus, dysbindin is essential for adaptive neural plasticity and may link altered homeostatic signaling with a complex neurological disease.
摘要
实现神经功能稳态稳定的分子机制在很大程度上仍然未知。为了更好地理解神经功能在发育过程中和整个生命过程中是如何稳定的，我们使用了基于电生理学的正向遗传学筛选，并评估了250多个神经元表达基因在果蝇突触传递稳态调节中的作用。该筛选排除了许多突触蛋白的参与，并确定了与人类精神分裂症相关的基因失调结合蛋白的关键功能。我们发现，失调结合蛋白在突触前对于神经传递的逆行、稳态调节是必需的，并且在钙内流的下游以剂量依赖的方式发挥作用或独立于钙内流发挥作用。因此，失调结合蛋白对于适应性神经可塑性至关重要，并且可能将改变的稳态信号与一种复杂的神经系统疾病联系起来。
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