Nuclear translocation and transcription regulation by the membrane-associated guanylate kinase CASK/LIN-2

• Published in: Nature (London) 2000-03, Vol.404 (6775), p.298-302
• Main Authors: Sheng, Morgan, Hsueh, Yi-Ping, Wang, Ting-Fang, Yang, Fu-Chia
• Format: Article
• Language: English
• Subjects: Animals; Binding Sites; Biological and medical sciences; Biological Transport; Brain; Caenorhabditis elegans; Calcium-Calmodulin-Dependent Protein Kinases; CASK protein; Cell Adhesion Molecules, Neuronal - metabolism; Cell differentiation, maturation, development, hematopoiesis; Cell Nucleus - metabolism; Cell physiology; Cells, Cultured; Cerebral Cortex - embryology; Cerebral Cortex - physiology; COS Cells; DNA - metabolism; DNA-Binding Proteins - metabolism; Extracellular Matrix Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Genes, Reporter; Guanylate Kinases; Helminth Proteins - metabolism; Hippocampus - cytology; Humanities and Social Sciences; letter; Membrane Proteins - metabolism; Membranes; Mice; Molecular and cellular biology; Molecular Sequence Data; multidisciplinary; Nerve Tissue Proteins; Neurology; Neurons - metabolism; Nucleoside-Phosphate Kinase - metabolism; Protein Binding; Proteins; Rats; Regulatory Sequences, Nucleic Acid; Science; Science (multidisciplinary); Serine Endopeptidases; Tbr-1 gene; Transcription Factors - physiology; Transcription, Genetic; Translocation
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/35005118

Membrane-associated guanylate kinases (MAGUKs) contain multiple protein-binding domains that allow them to assemble specific multiprotein complexes in particular regions of the cell. CASK/LIN-2, a MAGUK required for EGF receptor localization and signalling in Caenorhabditis elegans, contains a calmodulin-dependent protein kinase-like domain followed by PDZ, SH3 and guanylate kinase-like domains. In adult rat brain, CASK is concentrated at neuronal synapses and binds to the cell-surface proteins neurexin and syndecan and the cytoplasmic proteins Mint/LIN-10 and Veli/LIN-7 (refs 4, 9, 10). Here we report that, through its guanylate kinase domain, CASK interacts with Tbr-1, a T-box transcription factor that is involved in forebrain development. CASK enters the nucleus and binds to a specific DNA sequence (the T-element) in a complex with Tbr-1. CASK acts as a coactivator of Tbr-1 to induce transcription of T-element containing genes, including reelin, a gene that is essential for cerebrocortical development. Our findings show that a MAGUK which is usually associated with cell junctions has a transcription regulation function.