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• W2809416188 abstract "Synapse maturation is a neural activity–dependent process during brain development, in which active synapses preferentially undergo maturation to establish efficient neural circuits in the brain. Defects in this process are implicated in various neuropsychiatric disorders. We have previously reported that a postsynaptic transmembrane protein, signal regulatory protein-α (SIRPα), plays an important role in activity-dependently directing synapse maturation. In the presence of synaptic activity, the ectodomain of SIRPα is cleaved and released and then acts as a retrograde signal to induce presynaptic maturation. However, how SIRPα detects synaptic activity to promote its ectodomain cleavage and synapse maturation is unknown. Here, we show that activity-dependent tyrosine phosphorylation of SIRPα is critical for SIRPα cleavage and synapse maturation. We found that during synapse maturation and in response to neural activity, SIRPα is highly phosphorylated on its tyrosine residues in the hippocampus, a structure critical for learning and memory. Tyrosine phosphorylation of SIRPα was necessary for SIRPα cleavage and presynaptic maturation, as indicated by the fact that a phosphorylation-deficient SIRPα variant underwent much less cleavage and could not drive presynaptic maturation. However, SIRPα phosphorylation did not affect its synaptic localization. Finally, we show that inhibitors of the Src and JAK kinase family suppress neural activity–dependent SIRPα phosphorylation and cleavage. Together, our results indicate that SIRPα phosphorylation serves as a mechanism for detecting synaptic activity and linking it to the ectodomain cleavage of SIRPα, which in turn drives synapse maturation in an activity-dependent manner." @default.
• W2809416188 created "2018-06-29" @default.
• W2809416188 creator A5013307467 @default.
• W2809416188 creator A5041967567 @default.
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• W2809416188 date "2018-08-01" @default.
• W2809416188 modified "2023-10-12" @default.
• W2809416188 title "Tyrosine phosphorylation of the transmembrane protein SIRPα: Sensing synaptic activity and regulating ectodomain cleavage for synapse maturation" @default.
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• W2809416188 doi "https://doi.org/10.1074/jbc.ra117.001488" @default.
• W2809416188 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6078463" @default.
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