| 論文種別 | 原著(症例報告除く) |
| 言語種別 | 英語 |
| 査読の有無 | その他(不明) |
| 表題 | Neuronal activity drives PCDH9 cleavage and nuclear translocation to coordinate structural and functional remodeling. |
| 掲載誌名 | 正式名：Frontiers in cellular neuroscience 略 称：Front Cell Neurosci ISSNコード：16625102/16625102 |
| 巻・号・頁 | 19,pp.1736960 |
| 著者・共著者 | Federico Miozzo, Annalaura Zambrano Avendano, Maria Giuseppa Caso, Benedetta Valentino, Shinji Hirano, Luca Murru, Edoardo Moretto, Maria Passafaro |
| 発行年月 | 2026/01 |
| 概要 | Protocadherins are key regulators of neurodevelopment and synaptic function, acting not only as adhesion molecules but also as synaptic hubs for intracellular signaling. Here, we uncover a novel activity-dependent signaling pathway for Pcdh9, a protocadherin linked to Autism Spectrum Disorder and Major Depressive Disorder. By combining biochemical and immunohistochemistry approaches on neuronal cultures, we show that neuronal activity triggers Matrix Metalloproteases (MMP)-dependent cleavage of PCDH9, generating a C-terminal fragment (CTF) that translocates to the nucleus. PCDH9 CTF overexpression promotes dendritic growth, increases spine density, and concomitantly strengthens excitatory synaptic transmission. These findings identify PCDH9 CTF as a novel activity-dependent signaling molecule that links synaptic activity to structural remodeling and functional modulation, suggesting a new mechanism by which synaptic activity shapes neuronal properties. |
| DOI | 10.3389/fncel.2025.1736960 |
| PMID | 41685090 |