Mutations in Interleukin-1 receptor accessory protein-like 1 gene (IL1RAPL1) are responsible for mental retardation and associated with autism. Yoshida et al. in Mishina's lab revealed that IL1RAPL1 regulated synapse formation, one of the most important steps of neuronal network formation in the brain. IL1RAPL1 on the postsynaptic membrane interacted with protein tyrosine phosphatase (PTP) δ on the membrane of the presynaptic neurons to form trans-synaptic complex. The IL1RAPL1-PTPδ complex induced both pre- and postsynaptic differentiation. Furthermore, IL1RAPL1 selectively induced excitatory synapse formation. Our findings raise an intriguing possibility that the impairment of synapse formation may underlie certain forms of mental retardation and autism as a common pathogenic pathway shared by these mental disorders.

Program member
Masayoshi Mishina (Department of Functional Biology, Graduate School of Medicine)

IL1RAPL1 mediates synapse formation by trans-synaptic interaction with PTPδ.