Phosphoproteome Analysis Identifies a Synaptotagmin-1-associated complex involved in Ischemic Neuron Injury

Mol Cell Proteomics. 2022 Mar 4:100222. doi: 10.1016/j.mcpro.2022.100222. Online ahead of print.ABSTRACTCerebral stroke is one of the leading causes of death in adults worldwide. However, the molecular mechanisms of stroke-induced neuron injury are not fully understood. Here, we obtained phosphoproteomic and proteomic profiles of the acute ischemic hippocampus by LC-MS/MS analysis. Quantitative phosphoproteomic analyses revealed that the dysregulated phosphoproteins were involved in synaptic components and neurotransmission. We further demonstrated that phosphorylation of Synaptotagmin-1 (Syt1) at the Thr112 site in cultured hippocampal neurons aggravated oxygen-glucose deprivation (OGD)-induced neuronal injury. Immature neurons with low expression of Syt1 exhibit slight neuronal injury in a cerebral ischemia model. Administration of the Tat-Syt1T112A peptide protects neurons against cerebral ischemia-induced injury in vitro and in vivo. Surprisingly, potassium voltage-gated channel subfamily KQT member 2 (Kcnq2) interacted with Syt1 and Annexin A6 (Anxa6) and alleviated Syt1-mediated neuronal injury upon OGD treatment. These results reveal a mechanism underlying neuronal injury and may provide new targets for neuroprotection after acute cerebral ischemia onset.PMID:35257887 | DOI:10.1016/j.mcpro.2022.100222
Source: Molecular and Cellular Proteomics : MCP - Category: Molecular Biology Authors: Source Type: research