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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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AMP-Activated Protein Kinases / antagonists & inhibitors
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AMP-Activated Protein Kinases / genetics
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AMP-Activated Protein Kinases / metabolism*
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Animals
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Cell Adhesion Molecules / genetics
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Cell Adhesion Molecules / metabolism*
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Cells, Cultured
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HEK293 Cells
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Humans
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Mice
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Nerve Growth Factors / pharmacology*
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Netrin-1
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Neurites / physiology*
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Neurons / cytology
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Neurons / drug effects*
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Neurons / metabolism
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Phosphorylation
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Protein Binding
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Protein Kinase Inhibitors / pharmacology
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RNA Interference
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RNA, Small Interfering
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / genetics
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Signal Transduction / drug effects
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Transfection
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Tumor Suppressor Proteins / pharmacology*
Substances
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Cell Adhesion Molecules
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DSCAM protein, human
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NTN1 protein, human
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Nerve Growth Factors
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Ntn1 protein, mouse
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Protein Kinase Inhibitors
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RNA, Small Interfering
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Recombinant Fusion Proteins
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Tumor Suppressor Proteins
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Netrin-1
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PRKAG1 protein, human
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AMP-Activated Protein Kinases