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

Merel J.W. Adjobo-Hermans, Kevin C. Crosby, Mateusz Putyrski, Arshia Bhageloe, Laura van Weeren, Carsten Schultz, Joachim Goedhart, Theodorus W.J. Gadella

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)255-263
Number of pages9
JournalCellular Signalling
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2013

Keywords

  • Chemical dimerizers
  • FRET
  • Gαq
  • PLCβ

ASJC Scopus subject areas

  • Cell Biology

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    Adjobo-Hermans, M. J. W., Crosby, K. C., Putyrski, M., Bhageloe, A., van Weeren, L., Schultz, C., Goedhart, J., & Gadella, T. W. J. (2013). PLCβ isoforms differ in their subcellular location and their CT-domain dependent interaction with Gαq. Cellular Signalling, 25(1), 255-263. https://doi.org/10.1016/j.cellsig.2012.09.022