| First Author | Yoshida T | Year | 2012 |
| Journal | J Neurosci | Volume | 32 |
| Issue | 8 | Pages | 2588-600 |
| PubMed ID | 22357843 | Mgi Jnum | J:182360 |
| Mgi Id | MGI:5315316 | Doi | 10.1523/JNEUROSCI.4637-11.2012 |
| Citation | Yoshida T, et al. (2012) Interleukin-1 receptor accessory protein organizes neuronal synaptogenesis as a cell adhesion molecule. J Neurosci 32(8):2588-600 |
| abstractText | 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) delta through the extracellular domain. Mini-exon peptides in the Ig-like domains of PTPdelta splice variants were critical for their efficient binding to IL-1RAcP. The synaptogenic activities of IL-1RAcP isoforms were diminished in cortical neurons from PTPdelta knock-out mice. Correspondingly, PTPdelta 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. |
