5-HT2A receptor signalling through phospholipase D1 associated with its C-terminal tail

Zoë Barclay, Louise Dickson, Derek N Robertson, Melanie S Johnson, Pamela J Holland, Roberta Rosie, Liting Sun, Sue Fleetwood-Walker, Eve M Lutz, Rory Mitchell

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The 5-HT2AR (5-hydroxytryptamine-2A receptor) is a GPCR (G-protein-coupled receptor) that is implicated in the actions of hallucinogens and represents a major target of atypical antipsychotic agents. In addition to its classical signalling though PLC (phospholipase C), the receptor can activate several other pathways, including ARF (ADP-ribosylation factor)-dependent activation of PLD (phospholipase D), which appears to be achieved through a mechanism independent of heterotrimeric G-proteins. In the present study we show that wild-type and inactive constructs of PLD1 (but not PLD2) respectively facilitate and inhibit ARF-dependent PLD signalling by the 5-HT2AR. Furthermore we demonstrate that PLD1 specifically co-immunoprecipitates with the receptor and binds to a distal site in GST (glutathione transferase) fusion protein constructs of its C-terminal tail which is distinct from the ARF-interaction site, thereby suggesting the existence of a functional ARF-PLD signalling complex directly associated with this receptor. This reveals the spatial co-ordination of an important GPCR, transducer and effector into a physical complex that is likely to reinforce the impact of receptor activation on a heterotrimeric G-protein-independent signalling pathway. Signalling of this receptor through such non-canonical pathways may be important to its role in particular disorders.
LanguageEnglish
Pages651-60
Number of pages10
JournalBiochemical Journal
Volume436
Issue number3
DOIs
Publication statusPublished - 2011

Fingerprint

ADP-Ribosylation Factors
Receptor, Serotonin, 5-HT2A
Phospholipase D
Heterotrimeric GTP-Binding Proteins
Serotonin Receptors
G-Protein-Coupled Receptors
Serotonin
Hallucinogens
Chemical activation
Type C Phospholipases
Glutathione Transferase
Transducers
Antipsychotic Agents
Fusion reactions
phospholipase D1
Proteins

Keywords

  • ribosylation factors
  • amino acid sequence
  • animals
  • cos cells
  • cercopithecus aethiops
  • phospholipase D
  • receptor
  • signal transduction
  • serotonin

Cite this

Barclay, Z., Dickson, L., Robertson, D. N., Johnson, M. S., Holland, P. J., Rosie, R., ... Mitchell, R. (2011). 5-HT2A receptor signalling through phospholipase D1 associated with its C-terminal tail. Biochemical Journal, 436(3), 651-60. https://doi.org/10.1042/BJ20101844
Barclay, Zoë ; Dickson, Louise ; Robertson, Derek N ; Johnson, Melanie S ; Holland, Pamela J ; Rosie, Roberta ; Sun, Liting ; Fleetwood-Walker, Sue ; Lutz, Eve M ; Mitchell, Rory. / 5-HT2A receptor signalling through phospholipase D1 associated with its C-terminal tail. In: Biochemical Journal. 2011 ; Vol. 436, No. 3. pp. 651-60.
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Barclay, Z, Dickson, L, Robertson, DN, Johnson, MS, Holland, PJ, Rosie, R, Sun, L, Fleetwood-Walker, S, Lutz, EM & Mitchell, R 2011, '5-HT2A receptor signalling through phospholipase D1 associated with its C-terminal tail' Biochemical Journal, vol. 436, no. 3, pp. 651-60. https://doi.org/10.1042/BJ20101844

5-HT2A receptor signalling through phospholipase D1 associated with its C-terminal tail. / Barclay, Zoë; Dickson, Louise; Robertson, Derek N; Johnson, Melanie S; Holland, Pamela J; Rosie, Roberta; Sun, Liting; Fleetwood-Walker, Sue; Lutz, Eve M; Mitchell, Rory.

In: Biochemical Journal, Vol. 436, No. 3, 2011, p. 651-60.

Research output: Contribution to journalArticle

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AU - Barclay, Zoë

AU - Dickson, Louise

AU - Robertson, Derek N

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AU - Holland, Pamela J

AU - Rosie, Roberta

AU - Sun, Liting

AU - Fleetwood-Walker, Sue

AU - Lutz, Eve M

AU - Mitchell, Rory

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KW - cercopithecus aethiops

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KW - receptor

KW - signal transduction

KW - serotonin

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JO - Biochemical Journal

T2 - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 3

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Barclay Z, Dickson L, Robertson DN, Johnson MS, Holland PJ, Rosie R et al. 5-HT2A receptor signalling through phospholipase D1 associated with its C-terminal tail. Biochemical Journal. 2011;436(3):651-60. https://doi.org/10.1042/BJ20101844