| المؤلفون: |
Phadke RA; Molecular Biology, Cell Biology & Biochemistry Program, Boston University, Boston, MA, USA., Kruzich E; Neurobiology Section in the Department of Biology, Boston University, Boston, MA, USA., Fournier LA; Neurobiology Section in the Department of Biology, Boston University, Boston, MA, USA., Brack A; Molecular Biology, Cell Biology & Biochemistry Program, Boston University, Boston, MA, USA., Sha M; Neurobiology Section in the Department of Biology, Boston University, Boston, MA, USA., Picard I; Neurobiology Section in the Department of Biology, Boston University, Boston, MA, USA., Johnson C; Neurobiology Section in the Department of Biology, Boston University, Boston, MA, USA., Stroumbakis D; Neurobiology Section in the Department of Biology, Boston University, Boston, MA, USA., Salgado M; Neurobiology Section in the Department of Biology, Boston University, Boston, MA, USA., Yeung C; Neurobiology Section in the Department of Biology, Boston University, Boston, MA, USA., Escude Velasco B; Neurobiology Section in the Department of Biology, Boston University, Boston, MA, USA., Liu YY; Neurobiology Section in the Department of Biology, Boston University, Boston, MA, USA., Cruz-Martín A; Molecular Biology, Cell Biology & Biochemistry Program, Boston University, Boston, MA, USA.; Neurobiology Section in the Department of Biology, Boston University, Boston, MA, USA. |
| مستخلص: |
During development, activation of the complement pathway, an extracellular proteolytic cascade, results in microglia-dependent synaptic elimination via complement receptor 3 (CR3). Here, we report that decreased connectivity caused by overexpression of C4 (C4-OE), a schizophrenia-associated gene, is CR3 independent. Instead, C4-OE triggers GluR1 degradation through an intracellular mechanism involving endosomal trafficking protein SNX27, resulting in pathological synaptic loss. Moreover, the connectivity deficits associated with C4-OE were rescued by increasing levels of SNX27, linking excessive complement activity to an intracellular endolysosomal recycling pathway affecting synapses. |
