Very pleased to see the publication of the results of an outstanding collaborative projects with Gkogkas group at Foundation for Research & Technology Hellas and Khoutorsky group at McGill University in the Journal Brain.
In this paper, entitled "Mnk1/2 kinases regulate memory and autism-related behaviours via Syngap1”, by investigating the phosphoproteome regulated by Mnk kinases, we revealed a novel mechanism of translational control in brain implicating Mnk kinases and the autism risk gene Syngap1 in regulating memory and autism-related behaviours.
More specifically,
- We show that downstream of the MAPK pathway, Mnk1/2 are required for synaptic plasticity (LTP), learning and memory formation using a transgenic knockout model.
- We define the total and synaptic translatome regulated by Mnk1/2 using ribosome profiling.
- We define the Mnk1/2-regulated total and synaptic phosphoproteome in mouse brain, revealing a pervasive regulation of synaptic proteins and autism risk genes, including Syngap1 (S788).
- We show that Mnk1, the predominant Mnk in brain, binds to Syngap1 and that phosphorylation of Syngap1 S788 by Mnks promotes protein synthesis.
- Finally, we further elaborate the Mnk-Syngap1 link by rescue experiments in transgenic mice correcting memory deficits, social behaviour and mTORC1 signalling.