Excitatory neuron–specific SHP2-ERK signaling network regulates synaptic plasticity and memory

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Science Signaling  05 Mar 2019:
Vol. 12, Issue 571, eaau5755
DOI: 10.1126/scisignal.aau5755

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Cell type–specific RASopathy

The neurodevelopmental disorder Noonan syndrome is often caused by activating mutations in the phosphatase SHP2 that enhance RAS signaling. However, SHP2 is present in multiple neuron types as well as glia; thus, where the mutant protein has its pathological effects is unclear. Ryu et al. examined one NS-associated SHP2 mutation in isolated cell types from mice and determined that its presence in only excitatory neurons resulted in electrophysiological and cognitive effects. This was because certain adaptor proteins that interact with SHP2 to mediate RAS signaling are abundant in excitatory but not inhibitory neurons. These findings reveal that cell type–specific variations within the RAS signaling network underlie the phenotypes of NS and possibly other “RASopathies”.