Co-localization of Pirt protein and P2X2 receptors in the mouse enteric nervous system

Guo, Wei; Sui, Qian-Qian; Gao, Xiaofei; Feng, Jifeng; Zhu, Junjun; He, Cheng; Knight, Gillian E.; Burnstock, Geoffrey; Xiang, Zhenghua

doi:10.1007/s11302-016-9515-6

Cited by 8 publications

(7 citation statements)

References 30 publications

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“…The heart and neural crest derivatives expressed 1 (HAND1), belonging to the basic helix-loop-helix family of transcription factors, is showed to be a tumor suppressor gene in colorectal cancer [64]. Phosphoinositide interacting regulator of transient receptor potential channels (PIRT) was already described in various regions of the gastrointestinal tract of the adult mouse [65]. Regarding the lncRNAs, RP11-1336O20.2 is the only lncRNA that has been described in colon cancer tissue [66].…”

Section: Discussionmentioning

confidence: 99%

Portrait of Tissue-Specific Coexpression Networks of Noncoding RNAs (miRNA and lncRNA) and mRNAs in Normal Tissues

Cava

Bertoli

Castiglioni

2019

Computational and Mathematical Methods in Medicine

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Genes that encode proteins playing a role in more than one biological process are frequently dependent on their tissue context, and human diseases result from the altered interplay of tissue- and cell-specific processes. In this work, we performed a computational approach that identifies tissue-specific co-expression networks by integrating miRNAs, long-non-coding RNAs, and mRNAs in more than eight thousands of human samples from thirty normal tissue types. Our analysis (1) shows that long-non coding RNAs and miRNAs have a high specificity, (2) confirms several known tissue-specific RNAs, and (3) identifies new tissue-specific co-expressed RNAs that are currently still not described in the literature. Some of these RNAs interact with known tissue-specific RNAs or are crucial in key cancer functions, suggesting that they are implicated in tissue specification or cell differentiation.

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Section: Discussionmentioning

confidence: 99%

Portrait of Tissue-Specific Coexpression Networks of Noncoding RNAs (miRNA and lncRNA) and mRNAs in Normal Tissues

Cava

Bertoli

Castiglioni

2019

Computational and Mathematical Methods in Medicine

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“…Like PIRT, Tmem100 is a small two-span membrane protein and is evolutionarily related to PIRT with 27% sequence identity between the human paralogs. In addition to TRP channel function being modulated by proteins like TRP channel-associated factors and PIRTs, there is emerging evidence that PIRT is an endogenous regulator of P2X purinergic receptors (16,33). As with TRP channels, P2X receptors are considered promising therapeutic targets and highlight the possibility of developing therapeutics based on targeting modulatory proteins such as PIRT.…”

Section: Species-dependent Modulation Of Trpm8 By Pirtmentioning

confidence: 99%

Phosphoinositide-interacting regulator of TRP (PIRT) has opposing effects on human and mouse TRPM8 ion channels

Hilton

Salehpour

Sisco

et al. 2018

Journal of Biological Chemistry

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Transient receptor potential melastatin 8 (TRPM8) is a cold-sensitive ion channel with diverse physiological roles. TRPM8 activity is modulated by many mechanisms, including an interaction with the small membrane protein phosphoinositide-interacting regulator of TRP (PIRT). Here, using comparative electrophysiology experiments, we identified species-dependent differences between the human and mouse TRPM8-PIRT complexes. We found that human PIRT attenuated human TPRM8 conductance, unlike mouse PIRT, which enhanced mouse TRPM8 conductance. Quantitative Western blot analysis demonstrates that this effect does not arise from decreased trafficking of TRPM8 to the plasma membrane. Chimeric human/mouse TRPM8 channels were generated to probe the molecular basis of the PIRT modulation, and the effect was recapitulated in a pore domain chimera, demonstrating the importance of this region for PIRT-mediated regulation of TRPM8. Moreover, recombinantly expressed and purified human TRPM8 S1-S4 domain (comprising transmembrane helices S1-S4, also known as the sensing domain, ligand-sensing domain, or voltage sensing-like domain) and full-length human PIRT were used to investigate binding between the proteins. NMR experiments, supported by a pulldown assay, indicated that PIRT binds directly and specifically to the TRPM8 S1-S4 domain. Binding became saturated as the S1-S4:PIRT mole ratio approached 1. Our results have uncovered species-specific TRPM8 modulation by PIRT. They provide evidence for a direct interaction between PIRT and the TRPM8 S1-S4 domain with a 1:1 binding stoichiometry, suggesting that a functional tetrameric TRPM8 channel has four PIRT-binding sites.

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“…Beside the importance of the P2X7R in the gastrointestinal diseases described in literature, recent papers suggest that even other P2X subtypes could play a relevant role the gastrointestinal pathophysiology ( Paulino et al, 2011 ; Weng et al, 2015 ; Guo et al, 2016 ). Antagonists of the P2X3R showed promising activity in alleviating inflammatory and neuropathic pain in preclinical studies.…”

Section: P2 Purinergic Receptorsmentioning

confidence: 99%

Purinergic Ligands as Potential Therapeutic Tools for the Treatment of Inflammation-Related Intestinal Diseases

et al. 2018

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Inflammation-related intestinal diseases are a set of various conditions presenting an overactive enteric immune system. A continuous overproduction of pro-inflammatory cytokines and a decreased production of anti-inflammatory modulators are generally observed, while morpho-functional alterations of the enteric nervous system lead to intestinal secretory and motor dysfunctions. The factors at the basis of these conditions are still to be totally identified and current therapeutic strategies are aimed only at achieving and maintaining remission states, by using therapeutic tools like aminosalicylates, corticosteroids, immunomodulators, biological drugs (i.e., monoclonal antibodies), and eventually surgery. Recent reports described a key role of purinergic mediators (i.e., adenosine and its nucleotides ATP and ADP) in the regulation of the activity of immune cells and enteric nervous system, showing also that alterations of the purinergic signaling are linked to pathological conditions of the intestinal tract. These data prompted to a series of investigations to test the therapeutic potential for inflammation-related intestinal conditions of compounds able to restore or modulate an altered purinergic signaling within the gut. This review provides an overview on these investigations, describing the results of preclinical and/or clinical evaluation of compounds able to stimulate or inhibit specific P2 (i.e., P2X7) or P1 (i.e., A2A or A3) receptor signaling and to modify the adenosine levels through the modulation of enzymes activity (i.e., Adenosine Deaminase) or nucleoside transporters. Recent developments in the field are also reported and the most promising purine-based therapeutic strategies for the treatment of inflammation-related gastrointestinal disorders are schematically summarized.

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Co-localization of Pirt protein and P2X2 receptors in the mouse enteric nervous system

Cited by 8 publications

References 30 publications

Portrait of Tissue-Specific Coexpression Networks of Noncoding RNAs (miRNA and lncRNA) and mRNAs in Normal Tissues

Portrait of Tissue-Specific Coexpression Networks of Noncoding RNAs (miRNA and lncRNA) and mRNAs in Normal Tissues

Phosphoinositide-interacting regulator of TRP (PIRT) has opposing effects on human and mouse TRPM8 ion channels

Purinergic Ligands as Potential Therapeutic Tools for the Treatment of Inflammation-Related Intestinal Diseases

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