Interleukin-1 receptor accessory protein organizes neuronal synaptogenesis as a cell adhesion molecule.
Interleukin-1 receptor accessory protein (IL-1RAcP) is the essential component of receptor complexes mediating immune responses to interleukin-1 family cytokines. IL-1RAcP in the brain exists in two isoforms, IL-1RAcP and IL-1RAcPb, differing only in the C-terminal region. Here, we found robust synaptogenic activities of IL-1RAcP in cultured cortical neurons. Knockdown of ... IL-1RAcP isoforms in cultured cortical neurons suppressed synapse formation as indicated by decreases of active zone protein Bassoon puncta and dendritic protrusions. IL-1RAcP recovered the accumulation of presynaptic Bassoon puncta, while IL-1RAcPb rescued both Bassoon puncta and dendritic protrusions. Consistently, the expression of IL-1RAcP in cortical neurons enhances the accumulation of Bassoon puncta and that of IL-1RAcPb stimulated both Bassoon puncta accumulation and spinogenesis. IL-1RAcP interacted with protein tyrosine phosphatase (PTP) δ through the extracellular domain. Mini-exon peptides in the Ig-like domains of PTPδ splice variants were critical for their efficient binding to IL-1RAcP. The synaptogenic activities of IL-1RAcP isoforms were diminished in cortical neurons from PTPδ knock-out mice. Correspondingly, PTPδ required IL-1RAcPb to induce postsynaptic differentiation. Thus, IL-1RAcPb bidirectionally regulated synapse formation of cortical neurons. Furthermore, the spine densities of cortical and hippocampal pyramidal neurons were reduced in IL-1RAcP knock-out mice lacking both isoforms. These results suggest that IL-1RAcP isoforms function as trans-synaptic cell adhesion molecules in the brain and organize synapse formation. Thus, IL-1RAcP represents an interesting molecular link between immune systems and synapse formation in the brain.
Mesh Terms:
Amino Acids, Animals, Animals, Newborn, Cell Adhesion Molecules, Cells, Cultured, Cerebral Cortex, Coculture Techniques, Fibroblasts, Green Fluorescent Proteins, Humans, Interleukin-1 Receptor Accessory Protein, Mice, Mice, Knockout, Neural Cell Adhesion Molecules, Neurons, Presynaptic Terminals, Protein Binding, Protein Isoforms, Protein Structure, Tertiary, RNA, Small Interfering, Receptor-Like Protein Tyrosine Phosphatases, Class 4, Signal Transduction, Surface Plasmon Resonance, Synapses, Transfection, Vesicular Glutamate Transport Protein 1, Vesicular Inhibitory Amino Acid Transport Proteins
Amino Acids, Animals, Animals, Newborn, Cell Adhesion Molecules, Cells, Cultured, Cerebral Cortex, Coculture Techniques, Fibroblasts, Green Fluorescent Proteins, Humans, Interleukin-1 Receptor Accessory Protein, Mice, Mice, Knockout, Neural Cell Adhesion Molecules, Neurons, Presynaptic Terminals, Protein Binding, Protein Isoforms, Protein Structure, Tertiary, RNA, Small Interfering, Receptor-Like Protein Tyrosine Phosphatases, Class 4, Signal Transduction, Surface Plasmon Resonance, Synapses, Transfection, Vesicular Glutamate Transport Protein 1, Vesicular Inhibitory Amino Acid Transport Proteins
J. Neurosci.
Date: Feb. 22, 2012
PubMed ID: 22357843
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