Abstract
CASK acts as a coactivator for Tbr-1, an essential transcription factor in cerebral cortex development. Presently, the molecular mechanism of the CASK coactivation effect is unclear. Here, we report that CASK binds to another nuclear protein, CINAP, which binds histones and facilitates nucleosome assembly. CINAP, via its interaction with CASK, forms a complex with Tbr-1, regulating expression of the genes controlled by Tbr-1 and CASK, such as NR2b and reelin. A knockdown of endogenous CINAP in hippocampal neurons reduces the promoter activity of NR2b. Moreover, NMDA stimulation results in a reduction in the level of CINAP protein, via a proteasomal degradation pathway, correlating with a decrease in NR2b expression in neurons. This study suggests that reduction of the CINAP protein level by synaptic stimulation contributes to regulation of the transcriptional activity of the Tbr-1/CASK/CINAP protein complex and thus modifies expression of the NR2b gene.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Amino Acid Sequence
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Animals
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Blotting, Western / methods
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Carrier Proteins / physiology*
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Cells, Cultured
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Chlorocebus aethiops
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Chromatin / metabolism
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Cloning, Molecular
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Cycloheximide / pharmacology
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DNA-Binding Proteins / metabolism
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Embryo, Mammalian
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Excitatory Amino Acid Agonists / pharmacology
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Gene Expression Regulation* / drug effects
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Hippocampus / cytology
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Humans
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Indoles / metabolism
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Mice
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Models, Neurological
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Molecular Sequence Data
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Mutation
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N-Methylaspartate / pharmacology
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Nerve Tissue Proteins / metabolism*
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Nerve Tissue Proteins / physiology*
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Neuroblastoma
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Neurons / physiology
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Nuclear Proteins / metabolism*
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Nucleosomes / metabolism*
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Precipitin Tests / methods
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Protein Binding
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Protein Synthesis Inhibitors / pharmacology
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RNA, Antisense / metabolism
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RNA, Messenger / biosynthesis
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RNA, Small Interfering
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Rats
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Receptors, N-Methyl-D-Aspartate / metabolism
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Reelin Protein
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Reverse Transcriptase Polymerase Chain Reaction / methods
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T-Box Domain Proteins
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Time Factors
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Transcription Factors / metabolism*
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Transcription, Genetic / physiology*
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Two-Hybrid System Techniques
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Yeasts
Substances
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Adaptor Proteins, Signal Transducing
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CASKIN1 protein, human
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CINAP protein, mouse
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Carrier Proteins
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Chromatin
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DNA-Binding Proteins
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Excitatory Amino Acid Agonists
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Indoles
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NR2B NMDA receptor
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Nerve Tissue Proteins
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Nuclear Proteins
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Nucleosomes
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Protein Synthesis Inhibitors
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RNA, Antisense
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RNA, Messenger
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RNA, Small Interfering
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Receptors, N-Methyl-D-Aspartate
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Reelin Protein
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Reln protein, rat
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T-Box Domain Proteins
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Tbr1 protein, mouse
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Transcription Factors
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DAPI
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N-Methylaspartate
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Cycloheximide
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RELN protein, human
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Reln protein, mouse