The nervous system is one of the most complicated organ systems in invertebrates and vertebrates.Down syndrome cell adhesion molecule(DSCAM)of the immunoglobulin(Ig)superfamily is expressed widely in the nervous syste...The nervous system is one of the most complicated organ systems in invertebrates and vertebrates.Down syndrome cell adhesion molecule(DSCAM)of the immunoglobulin(Ig)superfamily is expressed widely in the nervous system during embryonic development.Previous studies in Drosophila suggest that Dscam plays important roles in neural development including axon branching,dendritic tiling and cell spacing.However,the function of the mammalian DSCAM gene in the formation of the nervous system remains unclear.Here,we show that Dscam^(del17) mutant mice exhibit severe hydrocephalus,decreased motor function and impaired motor learning ability.Our data indicate that the mammalian DSCAM gene is critical for the formation of the central nervous system.展开更多
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 w...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.展开更多
基金supported by grants from the Ministry of Science and Technology of China(Nos.2009CB825402 and 2010CB529603)National Natural Science Foundation of China(Grant No.30900845).
文摘The nervous system is one of the most complicated organ systems in invertebrates and vertebrates.Down syndrome cell adhesion molecule(DSCAM)of the immunoglobulin(Ig)superfamily is expressed widely in the nervous system during embryonic development.Previous studies in Drosophila suggest that Dscam plays important roles in neural development including axon branching,dendritic tiling and cell spacing.However,the function of the mammalian DSCAM gene in the formation of the nervous system remains unclear.Here,we show that Dscam^(del17) mutant mice exhibit severe hydrocephalus,decreased motor function and impaired motor learning ability.Our data indicate that the mammalian DSCAM gene is critical for the formation of the central nervous system.
基金supported by the National Basic Research Program(973 Program)(Nos.2010CB529603 and 2009CB825402)the National Natural Science Foundation of China(91132710)and Chinese Academy of Science(CASNN-GWPPS-2008)supported by NIH(RO1AG033004 and R56NS074763)and ALS Therapy Alliance.
文摘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.
