TRPV1 Activation Promotes β-arrestin2 Interaction with the Ribosomal Biogenesis Machinery in the Nucleolus: Implications for p53 Regulation and Neurite Outgrowth

Transient receptor potential vanilloids (TRPV1) are non-selective cation channels that sense and transduce inflammatory pain signals. We previously reported that activation of TRPV1 induced the translocation of β-arrestin2 (ARRB2) from the cytoplasm to the nucleus, raising questions about the functional role of ARRB2 in the nucleus. Here, we determined the ARRB2 nuclear signalosome by conducting a quantitative proteomic analysis of the nucleus-sequestered L395Q ARRB2 mutant, compared to the cytosolic wild-type ARRB2 (WT ARRB2), in a heterologous expression system. We identified clusters of proteins that localize to the nucleolus and are involved in ribosomal biogenesis. Accordingly, L395Q ARRB2 or WT ARRB2 after capsaicin treatment were found to co-localize and interact with the nucleolar marker nucleophosmin (NPM1), treacle protein (TCOF1) and RNA polymerase I (POL I). We further investigated the role of nuclear ARRB2 signaling in regulating neuroplasticity. Using neuroblastoma (neuro2a) cells and dorsal root ganglia (DRG) neurons, we found that L395Q ARRB2 mutant increased POL I activity, inhibited the tumor suppressorp53 (p53) level and caused a decrease in the outgrowth of neurites. Together, our results suggest that the activation of TRPV1 promotes the ARRB2-mediated regulation of ribosomal biogenesis in the nucleolus. The ARRB2-TCOF1-p53 checkpoint signaling pathway might be involved in regulating neurite outgrowth associated with pathological pain conditions.

• Publication year

  2021

• Venue

  International Journal of Molecular Sciences

• Publication date

  2021-02-25

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3390/ijms22052280PMID 33668926PMCID 7956682
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• β-Arrestins: Multitask Scaffolds Orchestrating the Where and When in Cell Signalling.

  2019cited by this paper
• POLR1B and neural crest cell anomalies in Treacher Collins syndrome type 4

  2019cited by this paper
• Changes in long-range rDNA-genomic interactions associate with altered RNA polymerase II gene programs during malignant transformation

  2019cited by this paper
• TRPV1 promotes opioid analgesia during inflammation

  2019cited by this paper
• Pre-Ribosomal RNA Processing in Human Cells: From Mechanisms to Congenital Diseases

  2018cited by this paper
• eIF4E-Dependent Translational Control: A Central Mechanism for Regulation of Pain Plasticity

  2018cited by this paper
• Multisite dependency of an E3 ligase controls monoubiquitylation-dependent cell fate decisions

  2018influential reference
• Structural plasticity and reorganisation in chronic pain

  2017cited by this paper
• Transient Receptor Potential Channels in neuropathic pain

  2017cited by this paper
• Translational Control Mechanisms in Persistent Pain.

  2017cited by this paper
• The MNK–eIF4E Signaling Axis Contributes to Injury-Induced Nociceptive Plasticity and the Development of Chronic Pain

  2017cited by this paper
• Structural plasticity and reorganisation in chronic pain

  2016cited by this paper
• The mechanism of μ-opioid receptor (MOR)-TRPV1 crosstalk in TRPV1 activation involves morphine anti-nociception, tolerance and dependence

  2015cited by this paper
• Cell fate determination by ubiquitin-dependent regulation of translation

  2015cited by this paper
• Treacher Collins syndrome TCOF1 protein cooperates with NBS1 in the DNA damage response

  2014cited by this paper
• Local translation and retrograde axonal transport of CREB regulates IL-6-induced nociceptive plasticity

  2014cited by this paper
• p53 Family and Cellular Stress Responses in Cancer

  2014cited by this paper
• Translational control in synaptic plasticity and cognitive dysfunction.

  2014cited by this paper
• Synaptic plasticity in pathological pain.

  2014cited by this paper
• Targeting RNA polymerase I with an oral small molecule CX-5461 inhibits ribosomal RNA synthesis and solid tumor growth.

  2011cited by this paper
• The balance between rRNA and ribosomal protein synthesis up- and downregulates the tumour suppressor p53 in mammalian cells

  2011cited by this paper
• The impact of pain in patients with polyneuropathy

  2011cited by this paper
• What is this thing called pain?

  2010cited by this paper
• NPM1/B23: A Multifunctional Chaperone in Ribosome Biogenesis and Chromatin Remodeling

  2010cited by this paper
• A 'garbage can' for ribosomes: how eukaryotes degrade their ribosomes.

  2010cited by this paper
• Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function

  2009cited by this paper
• The non‐apoptotic role of p53 in neuronal biology: enlightening the dark side of the moon

  2009cited by this paper
• Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function

  2008cited by this paper
• p53 in health and disease

  2007cited by this paper
• The multifunctional nucleolus

  2007cited by this paper
• Differential involvement of TRPV1 receptors at the central and peripheral nerves in CFA‐induced mechanical and thermal hyperalgesia

  2007cited by this paper
• Neurokinin-1 Receptor Enhances TRPV1 Activity in Primary Sensory Neurons via PKCε: A Novel Pathway for Heat Hyperalgesia

  2007cited by this paper
• Nucleophosmin Is Essential for Ribosomal Protein L5 Nuclear Export

  2006cited by this paper
• The tumor suppressor protein p53 is required for neurite outgrowth and axon regeneration

  2006cited by this paper
• Tcof1/Treacle is required for neural crest cell formation and proliferation deficiencies that cause craniofacial abnormalities

  2006cited by this paper
• Sensitization of TRPV1 by EP1 and IP reveals peripheral nociceptive mechanism of prostaglandins

  2005cited by this paper
• Synaptic plasticity and translation initiation.

  2004cited by this paper
• The Treacher Collins syndrome (TCOF1) gene product is involved in ribosomal DNA gene transcription by interacting with upstream binding factor.

  2004cited by this paper
• Proteomic Analysis of Human Nop56p-associated Pre-ribosomal Ribonucleoprotein Complexes

  2003cited by this paper
• Tumor suppressor ARF degrades B23, a nucleolar protein involved in ribosome biogenesis and cell proliferation.

  2003cited by this paper
• Differential Nucleocytoplasmic Shuttling of β-Arrestins

  2002cited by this paper
• Differential nucleocytoplasmic shuttling of beta-arrestins. Characterization of a leucine-rich nuclear export signal in beta-arrestin2.

  2002cited by this paper
• Potentiation of capsaicin receptor activity by metabotropic ATP receptors as a possible mechanism for ATP-evoked pain and hyperalgesia

  2001cited by this paper
• TCOF1 gene encodes a putative nucleolar phosphoprotein that exhibits mutations in Treacher Collins Syndrome throughout its coding region.

  1997cited by this paper
• What is this thing called pain

  1995cited by this paper
• The RNA polymerase I transcription factor, upstream binding factor, interacts directly with the TATA box-binding protein.

  1994cited by this paper

• Nucleophosmin 1 overexpression enhances neuroprotection by attenuating cellular stress in traumatic brain injury.

  2024cites this paper