Akt regulates the expression of MafK, synaptotagmin I, and syntenin-1, which play roles in neuronal function

Journal of Biomedical Science

Research

Young-Tae Ro¹  Eui U Park²  Chul Geun Kim³  Chan Young Shin⁴  Bo-Kwang Jang⁴  Sung-Il Yang⁵ 

[1] Department of Biochemistry, School of Medicine, Konkuk University, Seoul, Republic of Korea;Department of Forensic Medical Science, School of Medicine, Konkuk University, Seoul, Republic of Korea;Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, Republic of Korea;Department of Pharmacology, School of Medicine, Konkuk University, Seoul, Republic of Korea;Department of Pharmacology, School of Medicine, Konkuk University, Seoul, Republic of Korea;Research Institute of Medical Science, Konkuk University, Seoul, Republic of Korea;

关键词: Transcript Level;    PC12 Cell;    Nerve Growth Factor;    Neurite Outgrowth;    Neuronal Differentiation;   

DOI  :  10.1186/1423-0127-17-18

 received in 2009-12-01, accepted in 2010-03-17,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundAkt regulates various cellular processes, including cell growth, survival, and metabolism. Recently, Akt's role in neurite outgrowth has also emerged. We thus aimed to identify neuronal function-related genes that are regulated by Akt.MethodsWe performed suppression subtractive hybridization on two previously established PC12 sublines, one of which overexpresses the wild-type (WT) form and the other, the dominant-negative (DN) form of Akt. These sublines respond differently to NGF's neuronal differentiation effect.ResultsA variety of genes was identified and could be classified into several functional groups, one of which was developmental processes. Two genes involved in neuronal differentiation and function were found in this group. v-Maf musculoaponeurotic fibrosarcoma oncogene homolog K (MafK) induces the neuronal differentiation of PC12 cells and immature telencephalon neurons, and synaptotagmin I (SytI) is essential for neurotransmitter release. Another gene, syntenin-1 (Syn-1) was also recognized in the same functional group into which MafK and SytI were classified. Syn-1 has been reported to promote the formation of membrane varicosities in neurons. Quantitative reverse transcription polymerase chain reaction analyses show that the transcript levels of these three genes were lower in PC12 (WT-Akt) cells than in parental PC12 and PC12 (DN-Akt) cells. Furthermore, treatment of PC12 (WT-Akt) cells with an Akt inhibitor resulted in the increase of the expression of these genes and the improvement of neurite outgrowth. These results indicate that dominant-negative or pharmacological inhibition of Akt increases the expression of MafK, SytI, and Syn-1 genes. Using lentiviral shRNA to knock down endogenous Syn-1 expression, we demonstrated that Syn-1 promotes an increase in the numbers of neurites and branches.ConclusionsTaken together, these results indicate that Akt negatively regulates the expression of MafK, SytI, and Syn-1 genes that all participate in regulating neuronal integrity in some way or another.

【 授权许可】

Unknown   
© Ro et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.