Yamada Ryuji X, Matsuki Norio, Ikegaya Yuji
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan.
J Biol Chem. 2005 Nov 11;280(45):38020-8. doi: 10.1074/jbc.M503800200. Epub 2005 Sep 9.
Neurite polarity is a morphological characteristic of dentate gyrus granule cells, which extend axons to the hilar region and dendrites in the opposite direction, i.e. to the molecular layer. This remarkable polarity must require a differential system for axon and dendrite guidance. Here, we report that the axon and dendrites of a granule cell are differentially responsive to cAMP. In developing cultures of dispersed granule cells, dendritic growth cones were increased in number after pharmacological activation of cAMP signaling and decreased after blockade of cAMP signaling. Activation of cAMP signaling antagonized dendritic collapse induced by the potent repellents Sema3F and glutamate. In contrast to dendrites, axons were protected from Sema3F-induced collapse when cAMP signaling was inhibited. Axonal and dendritic growth cones both expressed type 1 adenylyl cyclase, but only axons showed a cAMP increase in response to Sema3F, and the elevated cAMP was sufficient to collapse axonal growth cones. Thus, the axons and dendrites of dentate granule cells differ in the regulation of cAMP levels as well as responsiveness to cAMP. cAMP may be crucial for shaping the information flow polarity in the dentate gyrus circuit.
神经突极性是齿状回颗粒细胞的一种形态学特征，这些细胞将轴突延伸至门区，而树突则向相反方向延伸，即向分子层延伸。这种显著的极性必然需要一个用于轴突和树突导向的差异系统。在此，我们报告颗粒细胞的轴突和树突对环磷酸腺苷（cAMP）有不同的反应。在分散颗粒细胞的发育培养物中，cAMP信号经药理学激活后，树突生长锥数量增加，而cAMP信号被阻断后数量减少。cAMP信号的激活拮抗了由强效排斥分子Sema3F和谷氨酸诱导的树突塌陷。与树突相反，当cAMP信号被抑制时，轴突受到保护，免受Sema3F诱导的塌陷。轴突和树突生长锥均表达1型腺苷酸环化酶，但只有轴突在对Sema3F作出反应时显示cAMP增加，而升高的cAMP足以使轴突生长锥塌陷。因此，齿状颗粒细胞的轴突和树突在cAMP水平的调节以及对cAMP的反应性方面存在差异。cAMP可能对塑造齿状回回路中的信息流极性至关重要。
