Modulation of M4 muscarinic acetylcholine receptors by interacting proteins

Ming Lei Guo, Li Min Mao, John Q. Wang

Research output: Contribution to journalReview article

7 Citations (Scopus)

Abstract

Protein-protein interactions represent an important mechanism for posttranslational modifications of protein expression and function. In brain cells, surface-expressed and membrane-bound neurotransmitter receptors are common proteins that undergo dynamic protein-protein interactions between their intracellular domains and submembranous regulatory proteins. Recently, the Gαi/o-coupled muscarinic M4 receptor (M4R) has been revealed to be one of these receptors. Through direct interaction with the intracellular loops or C-terminal tails of M4Rs, M4R interacting proteins (M4RIPs) vigorously regulate the efficacy of M4R signaling. A synapse-enriched protein kinase, Ca2+/calmodulin-dependent protein kinase II (CaMKII), exemplifies a prototype model of M4RIPs, and is capable of binding to the second intracellular loop of M4Rs. Through an activity- and phosphorylation-dependent mechanism, CaMKII potentiates the M4R/Gαi/o-mediated inhibition of M4R efficacy in inhibiting adenylyl cyclase and cAMP production. In striatal neurons where M4Rs are most abundantly expressed, M4RIPs dynamically control M4R activity to maintain a proper cholinergic tone in these neurons. This is critical for maintaining the acetylcholine-dopamine balance in the basal ganglia, which determines the behavioral responsiveness to dopamine stimulation by psychostimulants.

Original languageEnglish (US)
Pages (from-to)469-473
Number of pages5
JournalNeuroscience Bulletin
Volume26
Issue number6
DOIs
StatePublished - Dec 1 2010

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Receptor-Interacting Protein Serine-Threonine Kinases
Muscarinic Receptors
Proteins
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Dopamine
Muscarinic M4 Receptors
Neurons
Corpus Striatum
Neurotransmitter Receptor
Post Translational Protein Processing
Basal Ganglia
Adenylyl Cyclases
Synapses
Protein Kinases
Cholinergic Agents
Acetylcholine
Phosphorylation

Keywords

  • Ca/calmodulin-dependent protein kinase II
  • cocaine
  • dopamine
  • kinase
  • phosphorylation
  • striatum

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

Cite this

Modulation of M4 muscarinic acetylcholine receptors by interacting proteins. / Guo, Ming Lei; Mao, Li Min; Wang, John Q.

In: Neuroscience Bulletin, Vol. 26, No. 6, 01.12.2010, p. 469-473.

Research output: Contribution to journalReview article

Guo, Ming Lei ; Mao, Li Min ; Wang, John Q. / Modulation of M4 muscarinic acetylcholine receptors by interacting proteins. In: Neuroscience Bulletin. 2010 ; Vol. 26, No. 6. pp. 469-473.
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