Fig. 9: Summary of the findings of this study. | Communications Biology

Fig. 9: Summary of the findings of this study.

From: Post-ischemic ubiquitination at the postsynaptic density reversibly influences the activity of ischemia-relevant kinases

Fig. 9

a Post-ischemic detergent-resistant ubiquitination is elevated in neurons, particularly at the postsynaptic density (PSD) of glutamatergic neurons, while it is reduced in all other brain cell types. EC endothelial cell, glut glutamatergic, Tx Triton X100, Ub ubiquitination. b Postsynaptic proteins with increased ubiquitination after ischemic stroke include receptors (alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR), N-methyl-D-aspartate receptor (NMDAR), Densin-180, G protein-coupled receptor (GPCR), tropomyosin receptor kinase (TrkB)), scaffolding proteins and their adapters (brain-enriched guanylate kinase-associated protein (Begain), Disks large-associated protein 2–4 (Dlgap2-4), guanylate kinase-associated protein (GKAP), postsynaptic density protein 93/95 (PSD93/95), synapse-associated protein 97/102 (SAP97/102), SH3 and multiple ankyrin repeat domain (Shank)), G proteins (guanine nucleotide-binding protein G(i) subunit alpha (Gnai), guanine nucleotide-binding protein G(o) subunit alpha (Gnao), guanine nucleotide-binding protein G(s) subunit alpha isoforms short (Gnas), guanine nucleotide-binding protein G(t) subunit alpha (Gnat)), and signaling proteins (calcium-calmodulin-dependent protein kinase II (CaMKII), cyclin-dependent kinase 5 (Cdk5), creatine kinase b (CKb), Kalirin-7, protein kinase C (PKC), protein phosphatase 2 (PP2), phosphatase and TENsin homolog (Pten), proline-rich tyrosine kinase (Pyk2), synaptic Ras GTPase-activating protein 1 (SynGAP1)). c PSD-kinases, such as CaMKII, PKC, Cdk5, and Pyk2, are prominent post-ischemic ubiquitination targets. While CaMKII, PKC, and Cdk5 activities at the PSD are decreased after stroke, leading to reduced target phosphorylation, Pyk2 exhibits increased activity, thereby accelerating the phosphorylation of target proteins. In all cases, kinase activity regulation after stroke was dependent on ubiquitination, whose removal normalized activity. P phosphorylation. This figure was created with BioRender.com.

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