title: AMPK interacts with DSCAM and plays an important role in netrin-1 induced neurite outgrowth.
abstract: 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 its γ subunit, but does not interact with DCC (deleted in colorectal cancer), another major receptor for netrin-1. Netrin-treatment of cultured cortical neurons leads to increased phosphorylation of AMPK. Both AMPK mutant 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.
authors.affiliation: State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhu
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Chen
authors.forename: Jianghong
authors.initials: J
authors.lastname: Liu
authors.forename: Haihong
authors.initials: H
authors.lastname: Ye
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.forename: Jane Y
authors.initials: JY
authors.lastname: Wu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology*; D000075388:Netrin-1; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000494:pharmacology*
chemical_list: D015815:Cell Adhesion Molecules; C110833:DSCAM protein, human; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; C526222:PRKAG1 protein, human; D055372:AMP-Activated Protein Kinases