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Author Notes:

John Hepler: jhepler@emory.edu., Phone: (404) 727-3641.

The authors declare no competing financial interest.

Subjects:

Research Funding:

P.R.E. was supported by a predoctoral fellowship from the National Institutes of Health/National Institute of Neurological Disorders and Stroke (1F31NS086174).

J.R.H. was supported by grants from the National Institutes of Health/National Institute of Neurological Disorders and Stroke (5R01NS37112 and 1R21NS074975).

S.M.D. was supported by the Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health (Z01ES100221).

Research reported in this publication was supported in part by the Emory Neuroscience NINDS Core Facilities; and NIH/NIND Sunder award number P30NS055077.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemical Research Methods
  • Biochemistry & Molecular Biology
  • Regulator of G Protein Signaling 14 (RGS14)
  • calmodulin (CaM)
  • calcium (Ca2+)
  • Ca2+/calmodulin-dependent protein kinase II (CaMKII)
  • synapse
  • synaptic plasticity
  • long-term potentiation (LTP)
  • hippocampus CA2
  • interactome
  • learning and memory
  • GTPASE-ACTIVATING PROTEIN
  • VASOPRESSIN 1B RECEPTOR
  • LONG-TERM POTENTIATION
  • LARGE GENE LISTS
  • SYNAPTIC PLASTICITY
  • HUMAN BRAIN
  • AREA CA2
  • CALMODULIN
  • MEMORY
  • G-ALPHA(I)

Interactome Analysis Reveals Regulator of G Protein Signaling 14 (RGS14) is a Novel Calcium/Calmodulin (Ca2+/CaM) and CaM Kinase II (CaMKII) Binding Partner

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Journal Title:

Journal of Proteome Research

Volume:

Volume 17, Number 4

Publisher:

, Pages 1700-1711

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Regulator of G Protein Signaling 14 (RGS14) is a complex scaffolding protein that integrates G protein and MAPK signaling pathways. In the adult mouse brain, RGS14 is predominantly expressed in hippocampal CA2 neurons where it naturally inhibits synaptic plasticity and hippocampus-dependent learning and memory. However, the signaling proteins that RGS14 natively engages to regulate plasticity are unknown. Here, we show that RGS14 exists in a high-molecular-weight protein complex in brain. To identify RGS14 neuronal interacting partners, endogenous RGS14 immunoprecipitated from mouse brain was subjected to mass spectrometry and proteomic analysis. We find that RGS14 interacts with key postsynaptic proteins that regulate plasticity. Gene ontology analysis reveals the most enriched RGS14 interactors have functional roles in actin-binding, calmodulin(CaM)-binding, and CaM-dependent protein kinase (CaMK) activity. We validate these findings using biochemical assays that identify interactions with two previously unknown binding partners. We report that RGS14 directly interacts with Ca 2+ /CaM and is phosphorylated by CaMKII in vitro. Lastly, we detect that RGS14 associates with CaMKII and CaM in hippocampal CA2 neurons. Taken together, these findings demonstrate that RGS14 is a novel CaM effector and CaMKII phosphorylation substrate thereby providing new insight into mechanisms by which RGS14 controls plasticity in CA2 neurons.

Copyright information:

© 2018 American Chemical Society.

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