Stable G protein-effector complexes in striatal neurons: mechanism of assembly and role in neurotransmitter signaling

Elife. 2015 Nov 27;4:e10451. doi: 10.7554/eLife.10451.

Abstract

In the striatum, signaling via G protein-coupled neurotransmitter receptors is essential for motor control. Critical to this process is the effector enzyme adenylyl cyclase type 5 (AC5) that produces second messenger cAMP upon receptor-mediated activation by G protein Golf. However, the molecular organization of the Golf-AC5 signaling axis is not well understood. In this study, we report that in the striatum AC5 exists in a stable pre-coupled complex with subunits of Golf heterotrimer. We use genetic mouse models with disruption in individual components of the complex to reveal hierarchical order of interactions required for AC5-Golf stability. We further identify that the assembly of AC5-Golf complex is mediated by PhLP1 chaperone that plays central role in neurotransmitter receptor coupling to cAMP production motor learning. These findings provide evidence for the existence of stable G protein-effector signaling complexes and identify a new component essential for their assembly.

Keywords: G proteins; cAMP; cell biology; motor control; mouse; neuroscience; signal transduction; striatum.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / metabolism*
  • Animals
  • GTP-Binding Protein alpha Subunits / metabolism*
  • Mice
  • Neurons / enzymology*
  • Neurotransmitter Agents / metabolism*
  • Protein Multimerization*
  • Receptors, Neurotransmitter / metabolism*

Substances

  • GTP-Binding Protein alpha Subunits
  • Neurotransmitter Agents
  • Receptors, Neurotransmitter
  • olfactory G protein subunit alpha olf
  • Adenylyl Cyclases
  • adenylyl cyclase type V