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Rho-and Ca2+- dependent signaling mechanisms controlling neuronal actin cytoskeleton

控制神经元肌动蛋白细胞骨架的 Rho 和 Ca2 依赖性信号传导机制

基本信息

批准号：
13680842
负责人：
BITO Haruhiko
金额：
$ 2.3万
依托单位：
The University of Tokyo (2002)Kyoto University (2001)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13680842/
关键词：
Rho mDia cerebellar granule neurons axon neurite outgrowth calcium CaM kinase CREB calcium CaMキナーゼ actin シナプス成長円錐突起進展

项目摘要

1) Elucidation of the role of a Rho-target mDia in the regulation of axon elongationWe sought for Rho target molecules potentially involved in formation of polarity and bipolar axons out of the newly differentiated yet round cerebellar granule neurons in culture. Lipofection of various mutants revealed that 1) inhibition of ROCK activity promoted axon initiation and growth cone dynamics, and that 2) the adaptor mDia downstream of Rho rather promoted axon formation and elongation. Such experiments clearly demonstrated the necessity to orchestrate and coordinate the activity of several Rho effectors in order to achieve proper neurites. These findings are in press in J. Cell Biol.2) Molecular cloning and characterization of CLICK-III, a novel CaMK-Like CREB kinase candidate gene product.Activation of the transcription factor CREB is thought to play an important role in mediating long-term changes in neuronal properties by virtue of controlling activity-induced gene expression. We attempted to identify possible CaMKIV-related kinase with CREB phoshporylating activity. An isolated novel gene, CLICK-III, was activated in vitro by Ca2+/CaM, and was able to phosphorylate Ser-133 of CREB. CLICK-III expression was enriched in the limbic system and the midbrain, as revealed by in situ hybridization analyzes. This stands out from all published distribution of. Various other CaMK family members, and indicate the possibility that this kinase activity may possibly be involved in the activity of these nuclei. These findings are now in press in the J. Biol. Chem.

1)阐明Rho靶分子mDia在轴突伸长调控中的作用我们在培养的新分化的圆形小脑颗粒神经元中寻找可能参与极性和双极轴突形成的Rho靶分子。各种突变体的脂质体转染揭示：1）ROCK活性的抑制促进轴突起始和生长锥动力学，以及2）Rho下游的衔接子mDia反而促进轴突形成和伸长。这些实验清楚地表明，为了获得适当的神经突，有必要协调和协调几种Rho效应物的活性。2）新型CaMK样CREB激酶候选基因产物CLICK-III的分子克隆和表征。转录因子CREB的激活被认为通过控制活性诱导的基因表达在介导神经元特性的长期变化中起重要作用。我们试图鉴定可能与CREB磷酸化活性相关的CaMKIV激酶。一个分离的新基因，CLICK-III，在体外被Ca 2 +/CaM激活，并能够磷酸化CREB的Ser-133。原位杂交分析显示，CLICK-III表达在边缘系统和中脑中富集。这一点从所有出版的发行中脱颖而出。各种其他CaMK家族成员，并表明这种激酶活性可能参与这些细胞核的活性的可能性。这些发现现在正在《生物化学杂志》上发表。