LKB1 induces apical trafficking of Silnoon, a monocarboxylate transporter, in Drosophila melanogaster.
Silnoon (Sln) is a monocarboxylate transporter (MCT) that mediates active transport of metabolic monocarboxylates such as butyrate and lactate. Here, we identify Sln as a novel LKB1-interacting protein using Drosophila melanogaster genetic modifier screening. Sln expression does not affect cell cycle progression or cell size but specifically enhances LKB1-dependent apoptosis and tissue size reduction. Conversely, down-regulation of Sln suppresses LKB1-dependent apoptosis, implicating Sln as a downstream mediator of LKB1. The kinase activity of LKB1 induces apical trafficking of Sln in polarized cells, and LKB1-dependent Sln trafficking is crucial for triggering apoptosis induced by extracellular butyrate. Given that LKB1 functions to control both epithelial polarity and cell death, we propose Sln is an important downstream target of LKB1.
National Creative Research Initiatives Center for Cell Growth Regulation, Korea Advanced Institute of Science and Technology, Yusong-gu, Taejon 305-701, Korea.
Cholsoon
C
Jang
Gina
G
Lee
Jongkyeong
J
Chung
D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002087:Butyrates / Q000378:metabolism / Q000494:pharmacology; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005123:Eye / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D019344:Lactic Acid / Q000378:metabolism / Q000494:pharmacology; D007814:Larva / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D034622:RNA Interference; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology; D019895:Transposases / Q000235:genetics; D014921:Wings, Animal / Q000187:drug effects / Q000378:metabolism
D002087:Butyrates; D029721:Drosophila Proteins; D027501:Monocarboxylic Acid Transporters; C533179:Sln protein, Drosophila; D019344:Lactic Acid; D011494:Protein Kinases; C495775:LKB1 protein, Drosophila; D000091162:AMP-Activated Protein Kinase Kinases; D019895:Transposases