Dysbindin-1C Is Required for the Survival of Hilar Mossy Cells and the Maturation of Adult Newborn Neurons in Dentate Gyrus
Dysbindin-1C Is Required for the Survival of Hilar Mossy Cells and the Maturation of Adult Newborn Neurons in Dentate Gyrus
复制标题
Dysbindin-1C 是齿状回门部苔藓细胞存活和成年新生神经元成熟所必需的
DOI：
10.1074/jbc.m114.590927
复制
发表时间：
2014
影响因子：
4.8
通讯作者：
Li Wei
中科院分区：
文献类型：
--
作者：
Wang Hao;Yuan Yefeng;Zhang Zhao;Yan Hui;Feng Yaqin;Li Wei
DTNBP 1（dystrobrevin-binding protein 1）编码dysbindin-1，是精神分裂症的主要易感基因之一。dysbindin-1B和-1C亚型减少，但dysbindin-1A亚型在精神分裂症海马结构中没有变化，这表明dysbindin-1亚型在精神分裂症中可能具有不同的作用。我们发现，小鼠dysbindin-1C，而不是dysbindin-1A，是本地化的门海马齿状回的苔藓细胞。在dysbindin-1A和dysbindin-1C均缺失的桑迪（sdy）小鼠中，新生神经元的成熟率与野生型小鼠或dysbindin-1A不稳定但dysbindin-1C不变的静音（mu）小鼠相比显著延迟。Dysbindin-1C缺乏导致苔藓细胞减少，这导致新生神经元成熟延迟。这表明，dysbindin-1C，而不是dysbindin-1A，调节成人海马神经发生在非细胞自主的方式。
DTNBP1(dystrobrevin-binding protein 1), which encodes dysbindin-1, is one of the leading susceptibility genes for schizophrenia. Both dysbindin-1B and -1C isoforms are decreased, but the dysbindin-1A isoform is unchanged in schizophrenic hippocampal formation, suggesting dysbindin-1 isoforms may have distinct roles in schizophrenia. We found that mouse dysbindin-1C, but not dysbindin-1A, is localized in the hilar glutamatergic mossy cells of the dentate gyrus. The maturation rate of newborn neurons in sandy (sdy) mice, in which both dysbindin-1A and -1C are deleted, is significantly delayed when compared with that in wild-type mice or with that in muted (mu) mice in which dysbindin-1A is destabilized but dysbindin-1C is unaltered. Dysbindin-1C deficiency leads to a decrease in mossy cells, which causes the delayed maturation of newborn neurons. This suggests that dysbindin-1C, rather than dysbindin-1A, regulates adult hippocampal neurogenesis in a non-cell autonomous manner.