The intracellular domain of teneurin-2 has a nuclear function and represses zic-1-mediated transcription.
Teneurin-2, a vertebrate homologue of the Drosophila pair-rule gene ten-m/odz, is revealed to be a membrane-bound transcription regulator. In the nucleus, the intracellular domain of teneurin-2 colocalizes with promyelocytic leukemia (PML) protein in nuclear bodies implicated in transcription control. Since Drosophila ten-m acts epistatically to another pair-rule gene opa, we investigated whether gene regulation by the mammalian opa homologue zic-1 was influenced by the intracellular domain of teneurin-2. We found that zic-mediated transcription from the apolipoprotein E promoter was inhibited. Release of the intracellular domain of teneurin-2 could be stimulated by homophilic interaction of the extracellular domain, and the intracellular domain was stabilized by proteasome inhibitors. We have previously shown that teneurin-2 is expressed by neurons belonging to the same functional circuit. Therefore, we hypothesize that homophilic interaction enables neurons to identify their targets and that the release of the intracellular domain of teneurin-2 provides them with a signal to switch their gene expression program from growth towards differentiation once the proper contact has been made.
Bagutti
Claudia
C
Friedrich Miescher Institute, Novartis Forschungsstiftung, PO Box 2543, CH-4002 Basel, Switzerland.
Forro
Gaby
G
Ferralli
Jacqueline
J
Rubin
Beatrix
B
Chiquet-Ehrismann
Ruth
R
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D030161:Avian Proteins / Q000737:chemistry* / Q000502:physiology; D015153:Blotting, Western; D019556:COS Cells; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D003546:Cysteine Endopeptidases; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000502:physiology; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors; D009363:Neoplasm Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000502:physiology; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D000071156:Promyelocytic Leukemia Protein; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D025521:Tumor Suppressor Proteins; D001616:beta-Galactosidase / Q000378:metabolism
D001057:Apolipoproteins E; D030161:Avian Proteins; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C492123:ZIC1 protein, human; C402591:teneurin-2 protein, chicken; C067713:lactacystin; C070576:PML protein, human; D008156:Luciferases; D001616:beta-Galactosidase; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine