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. 2023 Apr 17;17:1154446. doi: 10.3389/fnins.2023.1154446

Figure 2.

Figure 2

Regulation of dendritic spine maturation in cortical neurons by DPYSL proteins through Sema3A-cdk5 signaling pathway. We propose a model involving the Sema3A-DPYSL pathway in the formation and maturation of dendritic spines. Fyn phosphorylates semaphorin receptor (Plexin A2) and facilitates PlexinA2 interaction to Sema3A. Fyn also promotes the phosphorylation of kinases like cyclin dependent kinase-5 (Cdk5) which in turn phosphorylates DPYSL proteins. We suggest that DPYSL proteins will thus play a role in the genesis and maturation of dendritic spines. AS an example, DPYSL1 can regulate spine development through Sema3A–Cdk5 signaling. Sema3A binds a receptor complex of the transmembrane proteins Neuropilin-1 (NP-1) and Plexin A1 (Plex-A1). After interacting with plexin A1, Fyn stimulates kinase activity of Cdk5 via Tyr15 phosphorylation of Tyr15. Cdk5 Tyr15 phosphorylation will then phosphorylates DPYSL1 tetramer at Thr509 and Ser522 locations. Sema3A through phosphorylation of DPYSL1 by Cdk5 will increase the density of PSD-95 and synapsin I clusters at dendrites and thus, promote formation of mature spines in cultured cortical primary neurons.