| First Author | Park H | Year | 2020 |
| Journal | EMBO J | Volume | 39 |
| Issue | 11 | Pages | e104150 |
| PubMed ID | 32347567 | Mgi Jnum | J:294829 |
| Mgi Id | MGI:6441563 | Doi | 10.15252/embj.2019104150 |
| Citation | Park H, et al. (2020) Splice-dependent trans-synaptic PTPdelta-IL1RAPL1 interaction regulates synapse formation and non-REM sleep. EMBO J 39(11):e104150 |
| abstractText | Alternative splicing regulates trans-synaptic adhesions and synapse development, but supporting in vivo evidence is limited. PTPdelta, a receptor tyrosine phosphatase adhering to multiple synaptic adhesion molecules, is associated with various neuropsychiatric disorders; however, its in vivo functions remain unclear. Here, we show that PTPdelta is mainly present at excitatory presynaptic sites by endogenous PTPdelta tagging. Global PTPdelta deletion in mice leads to input-specific decreases in excitatory synapse development and strength. This involves tyrosine dephosphorylation and synaptic loss of IL1RAPL1, a postsynaptic partner of PTPdelta requiring the PTPdelta-meA splice insert for binding. Importantly, PTPdelta-mutant mice lacking the PTPdelta-meA insert, and thus lacking the PTPdelta interaction with IL1RAPL1 but not other postsynaptic partners, recapitulate biochemical and synaptic phenotypes of global PTPdelta-mutant mice. Behaviorally, both global and meA-specific PTPdelta-mutant mice display abnormal sleep behavior and non-REM rhythms. Therefore, alternative splicing in PTPdelta regulates excitatory synapse development and sleep by modulating a specific trans-synaptic adhesion. |
