Native Piezo2 Interactomics Identifies Pericentrin as a Novel Regulator of Piezo2 in Somatosensory Neurons

Narayanan, Pratibha; Sondermann, Julia; Rouwette, Tom; Karaca, Samir; Urlaub, Henning; Mitkovski, Mišo; Gómez-Varela, David; Schmidt, Manuela

doi:10.1021/acs.jproteome.6b00235

Cited by 31 publications

(59 citation statements)

References 60 publications

(201 reference statements)

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“…In 2006, McCarter et al found that non‐specific cation influx mediated RA currents, while PIEZO2 has been identified to be the molecular basis for mediating RA currents in DRG neurons . In our study, the RA current induced by mechanical stimulation could be significantly blocked by the specific PIEZO2 blocker, FM1‐43.…”

Section: Discussionsupporting

confidence: 53%

Significance of piezo‐type mechanosensitive ion channel component 2 in premature ejaculation: An animal study

Chen

Yuan

et al. 2020

Andrology

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Background Penile hypersensitivity is one of the main pathological mechanisms of premature ejaculation. However, little is known about the neurophysiological mechanism of penile peripheral nerve sensitization. Piezo Type Mechanosensitive Ion Channel Component 2 (PIEZO2), was recently identified as a mechanically sensitive channel. Objectives This study explored the possible neural mechanisms of PIEZO2 action in the mechanisms of premature ejaculation using molecular biology and electrophysiology approaches. Materials and methods One hundred seventy male rats and 85 female rats were recruited. The females were induced estrus by injection of estradiol benzoate and progesterone followed by surgically castrated. Subsequently, the copulatory behaviors were record by a video camera six times, once a week. The last three mating processes of 134 male rats were successfully recorded. The males were divided into three groups according to ejaculation frequency value. Immunocytochemical and molecular methods as well as whole‐cell patch clamp recording were used to show the difference between premature ejaculation rats and control rats. To further clarify the involvement of PIEZO2 in premature ejaculation, we constructed a PIEZO2 knockdown model in rats by intrathecal injection of PIEZO2 antisense oligodeoxynucleotides. Results We showed that PIEZO2 in the penis head and in the dorsal root ganglia(DRG) were significantly increased in premature ejaculation rats. Whole‐cell patch clamp recording demonstrated that mechanical stimulation evoked a higher inward current density in premature ejaculation rats compared with control rats, which could be inhibited by the PIEZO2‐specific antagonist, FM1‐43. PIEZO2 knockdown experiments revealed that the inward current density induced by mechanical stimulation was significantly decreased in PIEZO2 knockdown rats, and that the mount frequency and ejaculation latency and frequency were significantly improved in PIEZO2 knockdown rats. Discussion and Conclusion Our data demonstrate PIEZO2 involvement in peripheral nerve sensitization, indicating that pharmacological antagonism of PIEZO2 may be a useful strategy for treating premature ejaculation.

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Section: Discussionsupporting

confidence: 53%

Significance of piezo‐type mechanosensitive ion channel component 2 in premature ejaculation: An animal study

Chen

Yuan

et al. 2020

Andrology

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“…However, our analysis has not been exhaustive as we did not examine all splice variants of Piezo2 and we did not investigate the potential interaction of Piezo2 with other membrane proteins. Other intracellular signaling pathways (Borbiro et al, 2015;Dubin et al, 2012) and protein interactions (Narayanan et al, 2016;Poole et al, 2014) have been shown to modulate Piezo2 function. More importantly, to fully appreciate the contribution of receptor diversification, it will be important to determine the in vivo consequences of Piezo2 splicing.…”

Section: Discussionmentioning

confidence: 99%

Cell Type Specific Splicing of Piezo2 Regulates Mechanotransduction

Szczot

Pogorzala

Solinski

et al. 2018

Biophysical Journal

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SummaryPiezo2 is a mechanically activated ion-channel required for touch discrimination, vibration detection and proprioception. Here we discovered that Piezo2 is extensively spliced, producing different Piezo2 isoforms with distinct properties. Sensory neurons from both mice and humans express a large repertoire of Piezo2 variants, while non-neuronal tissues express predominantly a single isoform. Notably, even within sensory ganglia, we demonstrate the splicing of Piezo2 to be cell-type specific. Biophysical characterization revealed substantial differences in ionpermeability, sensitivity to calcium modulation, and inactivation kinetics among Piezo2 splice variants. Together our results describe, at the molecular level, a potential mechanism by which transduction is tuned permitting the detection of a variety of mechanosensory stimuli. eTOC BlurbSzczot et al. find that the mechanoreceptor Piezo2 is extensively alternatively spliced generating multiple distinct isoforms. Their findings indicate that these splice products have specific tissue and cell-type expression patterns and exhibit differences in receptor properties.

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“…However, our analysis has not been exhaustive as we did not examine all splice variants of Piezo2 and we did not investigate the potential interaction of Piezo2 with other membrane proteins. Other intracellular signaling pathways (Borbiro et al, 2015; Dubin et al, 2012) and protein interactions (Narayanan et al, 2016; Poole et al, 2014) have been shown to modulate Piezo2 function. More importantly, to fully appreciate the contribution of receptor diversification, it will be important to determine the in vivo consequences of Piezo2 splicing.…”

Section: Discussionmentioning

confidence: 99%

Cell-Type-Specific Splicing of Piezo2 Regulates Mechanotransduction

et al. 2017

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Summary Piezo2 is a mechanically activated ion-channel required for touch discrimination, vibration detection and proprioception. Here we discovered that Piezo2 is extensively spliced, producing different Piezo2 isoforms with distinct properties. Sensory neurons from both mice and humans express a large repertoire of Piezo2 variants, while non-neuronal tissues express predominantly a single isoform. Notably, even within sensory ganglia, we demonstrate the splicing of Piezo2 to be cell-type specific. Biophysical characterization revealed substantial differences in ion-permeability, sensitivity to calcium modulation, and inactivation kinetics among Piezo2 splice variants. Together our results describe, at the molecular level, a potential mechanism by which transduction is tuned permitting the detection of a variety of mechanosensory stimuli.

show abstract

Native Piezo2 Interactomics Identifies Pericentrin as a Novel Regulator of Piezo2 in Somatosensory Neurons

Cited by 31 publications

References 60 publications

Significance of piezo‐type mechanosensitive ion channel component 2 in premature ejaculation: An animal study

Significance of piezo‐type mechanosensitive ion channel component 2 in premature ejaculation: An animal study

Cell Type Specific Splicing of Piezo2 Regulates Mechanotransduction

Cell-Type-Specific Splicing of Piezo2 Regulates Mechanotransduction

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