Institute of Neuroscience, State Key Laboratory of Neuroscience, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China 200031.
Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):469-74. doi: 10.1073/pnas.1321454111. Epub 2013 Dec 23.
Adult-born granule cells in the dentate gyrus of the rodent hippocampus are important for memory formation and mood regulation, but the cellular mechanism underlying their polarized development, a process critical for their incorporation into functional circuits, remains unknown. We found that deletion of the serine-threonine protein kinase LKB1 or overexpression of dominant-negative LKB1 reduced the polarized initiation of the primary dendrite from the soma and disrupted its oriented growth toward the molecular layer. This abnormality correlated with the dispersion of Golgi apparatus that normally accumulated at the base and within the initial segment of the primary dendrite, and was mimicked by disrupting Golgi organization via altering the expression of Golgi structural proteins GM130 or GRASP65. Thus, besides its known function in axon formation in embryonic pyramidal neurons, LKB1 plays an additional role in regulating polarized dendrite morphogenesis in adult-born granule cells in the hippocampus.
成年海马齿状回颗粒细胞对记忆形成和情绪调节很重要，但它们的极化发育的细胞机制尚不清楚，这个过程对它们整合到功能性回路至关重要。我们发现，丝氨酸-苏氨酸蛋白激酶 LKB1 的缺失或显性失活 LKB1 的过表达会减少从体细胞起始的主树突的极化起始，并破坏其向分子层的定向生长。这种异常与高尔基器的分散有关，高尔基器通常聚集在主树突的基部和起始段内，通过改变高尔基结构蛋白 GM130 或 GRASP65 的表达来破坏高尔基的组织，也可以模拟这种现象。因此，除了其在胚胎锥体神经元中的轴突形成中的已知功能外，LKB1 还在调节海马体中成年新生颗粒细胞的极化树突形态发生中发挥额外作用。
