Down syndrome cell adhesion molecule(DSCAM)acts as a netrin-1 receptor and mediates attractive response of axons to netrin-1 in neural development.However,the signaling mechanisms of netrin-DSCAM remain unclear.Here we report that AMP-activated protein kinase(AMPK)interacts with DSCAM through itsγsubunit,but does not interact with DCC(deleted in co-lorectal cancer),another major receptor for netrin-1.Netrin-treatment of cultured cortical neurons leads to increased phosphorylation of AMPK.Both AMPK mu-tant with dominant-negative effect and AMPK inhibitor can significantly suppress netrin-1 induced neurite outgrowth.Together,these findings demonstrate that AMPK interacts with DSCAM and plays an important role in netrin-1 induced neurite outgrowth.Our study uncovers a previously unknown component,AMPK,in netrin-DSCAM signaling pathway.
Kun ZhuXiaoping ChenJianghong LiuHaihong YeLi ZhuJane Y.Wu
Emerging studies support that RNA-binding proteins (RBPs) play critical roles in human biology and pathogenesis. RBPs are essential players in RNA processing and metabolism, including pre-mRNA splicing, polyadenylation, transport, surveillance, mRNA localization, mRNA stability control, translational control and editing of various types of RNAs. Aberrant expression of and mutations in RBP genes affect various steps of RNA processing, altering target gene function. RBPs have been associ- ated with various diseases, including neurological diseases. Here, we mainly focus on selected RNA-binding proteins including Nova-i/Nova-2, HuR/HuB/HuC/HuD, TDP-43, Fus, Rbfoxl/Rbfox2, QKI and FMRP, discussing their function and roles in human diseases.
ZHOU HuaLinMANGELSDORF MarieLIU JiangHongZHU LiWU Jane Y