School of Life Sciences, Tsinghua University, Beijing, 100084, China.
Sci China Life Sci. 2014 Jan;57(1):46-51. doi: 10.1007/s11427-013-4595-9. Epub 2014 Jan 9.
The Drosophila homolog of schizophrenia susceptibility gene dysbindin (Ddysb) affects a range of behaviors through regulation of multiple neurotransmitter signals, including dopamine activity. To gain insights into mechanisms underlying Ddysb-dependent regulation of dopamine signal, we investigated interaction between Ddysb and Ebony, the Drosophila β-alanyl-monoamine synthase involved in dopamine recycling. We found that Ddysb was capable of regulating expression of Ebony in a bi-directional manner and its subcellular distribution. Such regulation is confined to glial cells. The expression level of ebony and its accumulation in glial soma depend positively on Ddysb activity, whereas its distribution in glial processes is bound to be reduced in response to any alterations of Ddysb from the normal control level, either an increase or decrease. An optimal binding ratio between Dysb and Ebony might contribute to such non-linear effects. Thus, Ddysb-dependent regulation of Ebony could be one of the mechanisms that mediate dopamine signal.
果蝇精神分裂症易感性基因 dysbindin(Ddysb)的同源物通过调节多种神经递质信号(包括多巴胺活性)来影响一系列行为。为了深入了解 Ddysb 依赖调节多巴胺信号的机制,我们研究了 Ddysb 与 Ebony 之间的相互作用,Ebony 是一种参与多巴胺再循环的果蝇β-丙氨酸-单胺合酶。我们发现 Ddysb 能够双向调节 Ebony 的表达及其亚细胞分布。这种调节仅限于神经胶质细胞。Ebony 的表达水平及其在神经胶质细胞体中的积累依赖于 Ddysb 的活性,而其在神经胶质突起中的分布则必然会因 Ddysb 从正常对照水平的任何变化而减少,无论是增加还是减少。Dysb 和 Ebony 之间的最佳结合比可能有助于这种非线性效应。因此,Ddysb 对 Ebony 的调节可能是介导多巴胺信号的机制之一。