PLCβ isoforms differ in their subcellular location and their CT-domain dependent interaction with Gαq

Cell Signal. 2013 Jan;25(1):255-63. doi: 10.1016/j.cellsig.2012.09.022. Epub 2012 Sep 21.


Phospholipase C (PLC) β isoforms are implicated in various physiological processes and pathologies. However, mechanistic insight into the localization and activation of each of the isoforms is limited. Therefore, it is crucial to gain more in-depth knowledge as to the regulation of the different isoforms. Here we describe the subcellular location of full-length PLCβ isozymes and their C-terminal (CT) domains. Strikingly, we found isoforms PLCβ1 and PLCβ4 to be enriched at the plasma membrane, contrary to isoforms PLCβ2 and PLCβ3. We determined that the CT domain is an inhibitor of Gq-mediated increases in intracellular calcium, the potency of its effect being dependent upon the CT domain isoform used. Furthermore, ratiometric fluorescence resonance energy transfer (FRET) imaging was used to study the kinetics of the Gαq-CTβx interactions. By the use of recently developed tools, which enable the on-demand activation of Gαq, we could show that the interaction between constitutively active Gαq and PLCβ3 prolongs the residence time of PLCβ3 at the plasma membrane. These findings suggest that under physiological circumstances, PLCβ3 and Gαq interact in a kiss-and-run fashion, likely due to the GTPase-activating activity of PLCβ towards Gαq.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Signaling
  • Cell Membrane / metabolism
  • Cytosol / metabolism
  • Fluorescence Resonance Energy Transfer
  • GTP-Binding Protein alpha Subunits, Gq-G11 / antagonists & inhibitors
  • GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism*
  • HeLa Cells
  • Humans
  • Kinetics
  • Phospholipase C beta / chemistry
  • Phospholipase C beta / genetics
  • Phospholipase C beta / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Rats


  • Phospholipase C beta
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Calcium