Reciprocal regulation among TRPV1 channels and phosphoinositide 3-kinase in response to nerve growth factor

Stratiievska, Anastasiia; Nelson, Sara; Senning, Eric N.; Lautz, Jonathan D.; Smith, Stephen; Gordon, Sharona E.

doi:10.7554/elife.38869

Cited by 29 publications

(38 citation statements)

References 71 publications

(90 reference statements)

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“…4B and C). Both PI3K and MAPK activation has been reported to increase the activity of TRPV1 channels by increasing their surface expression (Ma et al, 2017;Stratiievska et al, 2018) but we found no evidence for increased Piezo2 trafficking to the plasma membrane in response to GABAB receptor activation (Fig. S3).…”

Section: Discussioncontrasting

confidence: 52%

Gi-Coupled Receptor Activation Potentiates Piezo2 Currents via Gβγ

Rosario

Yudin

et al. 2019

Preprint

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SUMMARYDysregulation of mechanosensitive Piezo2 channels is a hallmark of mechanical allodynia, yet the cellular mechanisms that sensitize mechanoreceptors are still poorly understood. Activation of Gi-coupled receptors sensitizes Piezo2 currents, but whether Gi-coupled receptors regulate the activity of Piezo2 channels is not known. Here, we found that activation of Gi-coupled receptors potentiates Piezo2 currents in dorsal root ganglion (DRG) neurons and in heterologous systems, but inhibits Piezo1 currents in heterologous systems. The potentiation, or inhibition of Piezo currents is abolished when blocking Gβγ with the c-terminal domain of the beta-adrenergic kinase (βARKct). Pharmacological inhibition of kinases downstream of Gβγ, phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK), also abolished the potentiation of Piezo2 currents. Hence, our studies illustrate an indirect mechanism of action of Gβγ to sensitize Piezo2 currents after activation of Gi-coupled receptors.

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Section: Discussioncontrasting

confidence: 52%

Gi-Coupled Receptor Activation Potentiates Piezo2 Currents via Gβγ

Rosario

Yudin

et al. 2019

Preprint

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“…However, whether EREG enhances TRPV1 activity through mechanisms such as transcriptional regulation, or by enhancing cell surface abundance, remain to be determined (Figure 3A). Similarly, NGF administration has also been reported to promote sensitization in part by inducing TRPV1 upregulation through a PI3K-dependent mechanism (Figure 3B) (Stein et al, 2006;Zhu and Oxford, 2007a;Stratiievska et al, 2018).…”

Section: Phosphatidylinositol 3-kinasementioning

confidence: 88%

Modulation of Pathological Pain by Epidermal Growth Factor Receptor

et al. 2021

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Chronic pain has been widely recognized as a major public health problem that impacts multiple aspects of patient quality of life. Unfortunately, chronic pain is often resistant to conventional analgesics, which are further limited by their various side effects. New therapeutic strategies and targets are needed to better serve the millions of people suffering from this devastating disease. To this end, recent clinical and preclinical studies have implicated the epidermal growth factor receptor signaling pathway in chronic pain states. EGFR is one of four members of the ErbB family of receptor tyrosine kinases that have key roles in development and the progression of many cancers. EGFR functions by activating many intracellular signaling pathways following binding of various ligands to the receptor. Several of these signaling pathways, such as phosphatidylinositol 3-kinase, are known mediators of pain. EGFR inhibitors are known for their use as cancer therapeutics but given recent evidence in pilot clinical and preclinical investigations, may have clinical use for treating chronic pain. Here, we review the clinical and preclinical evidence implicating EGFR in pathological pain states and provide an overview of EGFR signaling highlighting how EGFR and its ligands drive pain hypersensitivity and interact with important pain pathways such as the opioid system.

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“…LPA has been extensively linked to the generation of chronic neuropathic pain through its interactions with G protein-coupled receptors (GPCRs) [89][90][91][92] and to modulate the activity of several ion channels [93][94][95][96][97]. Regulation of the activity of TRPV1 by molecules of a lipidic nature has been explored, and it has been described that PIP 2 [98][99][100][101][102][103][104][105][106], polyunsaturated fatty acids (PUFAs) [107], monounsaturated fatty acids [108] and cholesterol [109][110][111] can modulate the activity of TRPV1, either directly or indirectly. However, reports of direct interactions of LPA with ion channels, in general, are scarce [95,112,113].…”

Section: Lysophosphatidic Acid: a Pain-producing Phospholipidmentioning

confidence: 99%

TRP ion channels: Proteins with conformational flexibility

et al. 2019

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Ion channels display conformational changes in response to binding of their agonists and antagonists. The study of the relationships between the structure and the function of these proteins has witnessed considerable advances in the last two decades using a combination of techniques, which include electrophysiology, optical approaches (i.e. patch clamp fluorometry, incorporation of non-canonic amino acids, etc.), molecular biology (mutations in different regions of ion channels to determine their role in function) and those that have permitted the resolution of their structures in detail (X-ray crystallography and cryo-electron microscopy). The possibility of making correlations among structural components and functional traits in ion channels has allowed for more refined conclusions on how these proteins work at the molecular level. With the cloning and description of the family of Transient Receptor Potential (TRP) channels, our understanding of several sensory-related processes has also greatly moved forward. The response of these proteins to several agonists, their regulation by signaling pathways as well as by protein-protein and lipid-protein interactions and, in some cases, their biophysical characteristics have been studied thoroughly and, recently, with the resolution of their structures, the field has experienced a new boom. This review article focuses on the conformational changes in the pores, concentrating on some members of the TRP family of ion channels (TRPV and TRPA subfamilies) that result in changes in their single-channel conductances, a phenomenon that may lead to fine-tuning the electrical response to a given agonist in a cell.

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Reciprocal regulation among TRPV1 channels and phosphoinositide 3-kinase in response to nerve growth factor

Cited by 29 publications

References 71 publications

Gi-Coupled Receptor Activation Potentiates Piezo2 Currents via Gβγ

Gi-Coupled Receptor Activation Potentiates Piezo2 Currents via Gβγ

Modulation of Pathological Pain by Epidermal Growth Factor Receptor

TRP ion channels: Proteins with conformational flexibility

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