Characterization of the interaction between the dopamine D4 receptor, KLHL12 and β-arrestins

Kamila Skieterska, Ao Shen, Dorien Clarisse, Pieter Rondou, Dasiel Oscar Borroto-Escuela, Béatrice Lintermans, Kjell Fuxe, Yang Kevin Xiang, Kathleen Van Craenenbroeck

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Dopamine receptors are G protein-coupled receptors involved in regulation of cognition, learning, movement and endocrine signaling. The action of G protein-coupled receptors is highly regulated by multifunctional proteins, such as β-arrestins which can control receptor desensitization, ubiquitination and signaling. Previously, we have reported that β-arrestin 2 interacts with KLHL12, a BTB-Kelch protein which functions as an adaptor in a Cullin3-based E3 ligase complex and promotes ubiquitination of the dopamine D4 receptor.Here, we have investigated the molecular basis of the interaction between KLHL12 and β-arrestins and questioned its functional relevance. Our data demonstrate that β-arrestin 1 and β-arrestin 2 bind constitutively to the most common dopamine D4 receptor polymorphic variants and to KLHL12 and that all three proteins can interact within a single macromolecular complex. Surprisingly, stimulation of the receptor has no influence on the association between these proteins or their cellular distribution.We found that Cullin3 also interacts with both β-arrestins but has no influence on their ubiquitination. Knockout of one of the two β-arrestins hampers neither interaction between the dopamine D4 receptor and KLHL12, nor ubiquitination of the receptor.Finally, our results indicate that p44/42 MAPK phosphorylation, the signaling pathway which is often regulated by β-arrestins is not influenced by KLHL12, but seems to be exclusively mediated by Gαi protein upon dopamine D4 receptor stimulation.

Original languageEnglish (US)
Pages (from-to)1001-1014
Number of pages14
JournalCellular Signalling
Volume28
Issue number8
DOIs
StatePublished - Aug 1 2016

Fingerprint

Arrestins
Dopamine D4 Receptors
Ubiquitination
G-Protein-Coupled Receptors
Proteins
Arrestin
Macromolecular Substances
Ubiquitin-Protein Ligases
Mitogen-Activated Protein Kinase 3
Dopamine Receptors
Cognition
Phosphorylation
Learning

Keywords

  • Dopamine D receptor
  • GPCR
  • KLHL12
  • Ubiquitination
  • β-arrestin

ASJC Scopus subject areas

  • Cell Biology

Cite this

Skieterska, K., Shen, A., Clarisse, D., Rondou, P., Borroto-Escuela, D. O., Lintermans, B., ... Van Craenenbroeck, K. (2016). Characterization of the interaction between the dopamine D4 receptor, KLHL12 and β-arrestins. Cellular Signalling, 28(8), 1001-1014. https://doi.org/10.1016/j.cellsig.2016.05.003

Characterization of the interaction between the dopamine D4 receptor, KLHL12 and β-arrestins. / Skieterska, Kamila; Shen, Ao; Clarisse, Dorien; Rondou, Pieter; Borroto-Escuela, Dasiel Oscar; Lintermans, Béatrice; Fuxe, Kjell; Xiang, Yang Kevin; Van Craenenbroeck, Kathleen.

In: Cellular Signalling, Vol. 28, No. 8, 01.08.2016, p. 1001-1014.

Research output: Contribution to journalArticle

Skieterska, K, Shen, A, Clarisse, D, Rondou, P, Borroto-Escuela, DO, Lintermans, B, Fuxe, K, Xiang, YK & Van Craenenbroeck, K 2016, 'Characterization of the interaction between the dopamine D4 receptor, KLHL12 and β-arrestins', Cellular Signalling, vol. 28, no. 8, pp. 1001-1014. https://doi.org/10.1016/j.cellsig.2016.05.003
Skieterska K, Shen A, Clarisse D, Rondou P, Borroto-Escuela DO, Lintermans B et al. Characterization of the interaction between the dopamine D4 receptor, KLHL12 and β-arrestins. Cellular Signalling. 2016 Aug 1;28(8):1001-1014. https://doi.org/10.1016/j.cellsig.2016.05.003
Skieterska, Kamila ; Shen, Ao ; Clarisse, Dorien ; Rondou, Pieter ; Borroto-Escuela, Dasiel Oscar ; Lintermans, Béatrice ; Fuxe, Kjell ; Xiang, Yang Kevin ; Van Craenenbroeck, Kathleen. / Characterization of the interaction between the dopamine D4 receptor, KLHL12 and β-arrestins. In: Cellular Signalling. 2016 ; Vol. 28, No. 8. pp. 1001-1014.
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