Korean J Physiol Pharmacol.  2020 Mar;24(2):129-135. 10.4196/kjpp.2020.24.2.129.

Connecting the dots between SHP2 and glutamate receptors

Affiliations
  • 1Department of Physiology, Seoul National University College of Medicine, Seoul 03080, Korea. yongseok7@snu.ac.kr
  • 2Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.
  • 3Neuroscience Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.

Abstract

SHP2 is an unusual protein phosphatase that functions as an activator for several signaling pathways, including the RAS pathway, while most other phosphatases suppress their downstream signaling cascades. The physiological and pathophysiological roles of SHP2 have been extensively studied in the field of cancer research. Mutations in the PTPN11 gene which encodes SHP2 are also highly associated with developmental disorders, such as Noonan syndrome (NS), and cognitive deficits including learning disabilities are common among NS patients. However, the molecular and cellular mechanism by which SHP2 is involved in cognitive functions is not well understood. Recent studies using SHP2 mutant mice or pharmacological inhibitors have shown that SHP2 plays critical role in learning and memory and synaptic plasticity. Here, we review the recent studies demonstrating that SHP2 is involved in synaptic plasticity, and learning and memory, by the regulation of the expression and/or function of glutamate receptors. We suggest that each cell type may have distinct paths connecting the dots between SHP2 and glutamate receptors, and these paths may also change with aging.

Keyword

AMPA receptor; Learning and memory; NMDA receptor; Rasopathy; Synaptic plasticity

MeSH Terms

Aging
Animals
Cognition
Cognition Disorders
Glutamic Acid*
Humans
Learning
Learning Disorders
Memory
Mice
Neuronal Plasticity
Noonan Syndrome
Phosphoric Monoester Hydrolases
Receptors, AMPA
Receptors, Glutamate*
Glutamic Acid
Phosphoric Monoester Hydrolases
Receptors, AMPA
Receptors, Glutamate
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