mTOR and MAPK: from localized translation control to epilepsy

BMC Neuroscience

Review

Bastian Popper¹  Helena F. Pernice¹  Michael A. Kiebler¹  Rico Schieweck¹ 

[1] Department of Anatomy and Cell Biology, Biomedical Center (BMC), Medical Faculty, Ludwig-Maximilians-University (LMU), Großhaderner Straße 9, 82152, Planegg-Martinsried, Germany;

关键词: RBP;    mTOR;    MAPK;    ERK;    Epilepsy;   

DOI  :  10.1186/s12868-016-0308-1

 received in 2016-06-29, accepted in 2016-11-09,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundEpilepsy is one of the most common neurological diseases characterized by excessive hyperexcitability of neurons. Molecular mechanisms of epilepsy are diverse and not really understood. All in common is the misregulation of proteins that determine excitability such as potassium and sodium channels as well as GABA receptors; which are all known as biomarkers for epilepsy. Two recently identified key pathways involve the kinases mechanistic target of rapamycin (mTOR) and mitogen-activated protein kinases (MAPK). Interestingly, mRNAs coding for those biomarkers are found to be localized at or near synapses indicating a local misregulation of synthesis and activity.ResultsResearch in the last decade indicates that RNA-binding proteins (RBPs) responsible for mRNA localization, stability and translation mediate local expression control. Among others, they are affected by mTOR and MAPK to guide expression of epileptic factors. These results suggest that mTOR/MAPK act on RBPs to regulate the fate of mRNAs, indicating a misregulation of protein expression at synapses in epilepsy.ConclusionWe propose that mTOR and MAPK regulate RBPs, thereby guiding the local expression of their target-mRNAs encoding for markers of epilepsy. Thus, misregulated mTOR/MAPK-RBP interplay may result in excessive local synthesis of ion channels and receptors thereby leading to hyperexcitability. Continuous stimulation of synapses further activates mTOR/MAPK pathway reinforcing their effect on RBP-mediated expression control establishing the basis for epilepsy. Here, we highlight findings showing the tight interplay between mTOR as well as MAPK with RBPs to control expression for epileptic biomarkers.

【 授权许可】

CC BY   
© The Author(s) 2016