Cell-Type-Specific Splicing of Piezo2 Regulates Mechanotransduction

Szczot, Marcin; Pogorzala, Leah A.; Solinski, Hans Jürgen; Young, Lynn; Yee, Philina; Pichon, Claire E. Le; Chesler, Alexander T.; Hoon, Mrinalini

doi:10.1016/j.celrep.2017.11.035

Cited by 102 publications

(77 citation statements)

References 50 publications

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“…A large number of channels are involved in mechanical sensing , including the Piezo channels . Piezo2 is expressed in many classes of peripheral sensory neurons and is the primary mechanotransducer channel for touch detection and proprioception in mice and humans . Also, changes in Piezo2 activity have been linked to mechanical hyperalgesia .…”

Section: Exogenous Triggersmentioning

confidence: 99%

Profiling of how nociceptor neurons detect danger – new and old foes

et al. 2019

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The host evolves redundant mechanisms to preserve physiological processing and homeostasis. These functions range from sensing internal and external threats, creating a memory of the insult and generating reflexes, which aim to resolve inflammation. Impairment in such functioning leads to chronic inflammatory diseases. By interacting through a common language of ligands and receptors, the immune and sensory nervous systems work in concert to accomplish such protective functions. Whilst this bidirectional communication helps to protect from danger, it can contribute to disease pathophysiology. Thus, the somatosensory nervous system is anatomically positioned within primary and secondary lymphoid tissues and mucosa to modulate immunity directly. Upstream of this interplay, neurons detect danger, which prompts the release of neuropeptides initiating (i) defensive reflexes (ranging from withdrawal response to coughing) and (ii) chemotaxis, adhesion and local infiltration of immune cells. The resulting outcome of such neuro‐immune interplay is still ill‐defined, but consensual findings start to emerge and support neuropeptides not only as blockers of TH1‐mediated immunity but also as drivers of TH2 immune responses. However, the modalities detected by nociceptors revealed broader than mechanical pressure and temperature sensing and include signals as various as cytokines and pathogens to immunoglobulins and even microRNAs. Along these lines, we aggregated various dorsal root ganglion sensory neuron expression profiling datasets supporting such wide‐ranging sensing capabilities to help identifying new danger detection modalities of these cells. Thus, revealing unexpected aspects of nociceptor neuron biology might prompt the identification of novel drivers of immunity, means to resolve inflammation and strategies to safeguard homeostasis.

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Section: Exogenous Triggersmentioning

confidence: 99%

Profiling of how nociceptor neurons detect danger – new and old foes

et al. 2019

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“…PIEZO2 is likely to display low conductance and be inactivated more promptly. Its key functions were mainly related to mechanosensation and proprioception in sensory neurons . While PIEZO1 protein was reported to associate with activation of integrin via R‐Ras mechanism .…”

Section: Introductionmentioning

confidence: 99%

PIEZO1 functions as a potential oncogene by promoting cell proliferation and migration in gastric carcinogenesis

Zhang

Zhou

Huang

et al. 2018

Molecular Carcinogenesis

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Gastric cancer (GC) is one of the most common malignancies in Asian areas. PIEZO1 has been implied to regulate epithelial homeostasis to play an important role in physiological processes. It is also related to tumor initiation and progression. However, the role of PIEZO1 has not yet been explored in GC. The expression of PIEZO1 in GC cell lines and primary samples was determined by qRT-PCR and Western blot. The clinical correlation of PIEZO1 in GC was evaluated by immunohistochemistry on tissue microarray. The oncogenic role of PIEZO1 was demonstrated in gastric tumorigenesis through a series of functional assays, including cell proliferation, cell invasion, and flow cytometry analysis. Drug sensitivity was also assessed by PIEZO1 knockdown experiment. PIEZO1 exhibited an upregulation in most of the GC cell lines and primary samples compared with non-tumorous gastric epithelial tissues. Increase of PIEZO1 was associated with poor disease specific survival. PIEZO1 knockdown led to inhibitory effect by suppressing cell proliferation and invasion and inhibiting xenograft formation. Decreased PIEZO1 enhanced the sensitivity of Cisplatin or 5-FU treatment. Morphological alteration was also observed in siPIEZO1 treated cells. GTP-Rac1 showed accumulated activated form, while total-RhoA was decreased accompanied with PIEZO1 knockdown. In the present study, PIEZO1 is required for cell proliferation, migration and invasion to promote GC progression. PIEZO1 also maintains cellular morphology related to GC cell motility by regulating the activity of Rho GTPase family members. Our data not only suggested a novel prognostic marker, but also provided a useful clinical therapeutic target for GC.

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“…Primer assays used in the present study. [63]. Sequence and exon-exon borders were provided by [63].…”

Section: Resultsmentioning

confidence: 99%

“…The primer pairs 1 and 4 are located on an alternatively spliced PIEZO2 variant, which is specific to neurons in mammals [63]. Primer pair 3 is specific for two PIEZO2 transcript variants including one that has not been exclusively described for neurons in mammals [63]. Transcript variant 1 was strongly expressed in AF and brain (~9200 to~12,000 copies/µg RNA) ( Figure 3).…”

Section: Genes Coding For Mechanoreceptor Proteins Were Expressed Inmentioning

confidence: 99%

“…The genes NTRK2, NTRK3, and GFRa2 encode neurotrophic receptors and were used in this study to distinguish between the different nerve types, as previously done in studies on mammalian models [32,33,43,45,63,67]. Neurotrophins control the differentiation and survival of nerve cells, whereby different classes of neurons depend on different neurotrophins [90].…”

Section: The Expression Of Neuron-and Glial-cell Markers Is Tissue-spmentioning

confidence: 99%

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Gene Profiling in the Adipose Fin of Salmonid Fishes Supports Its Function as a Flow Sensor

Koll

Ribera

Brunner

et al. 2019

Genes

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In stock enhancement and sea-ranching procedures, the adipose fin of hundreds of millions of salmonids is removed for marking purposes annually. However, recent studies proved the significance of the adipose fin as a flow sensor and attraction feature. In the present study, we profiled the specific expression of 20 neuron- and glial cell-marker genes in the adipose fin and seven other tissues (including dorsal and pectoral fin, brain, skin, muscle, head kidney, and liver) of the salmonid species rainbow trout Oncorhynchus mykiss and maraena whitefish Coregonus maraena. Moreover, we measured the transcript abundance of genes coding for 15 mechanoreceptive channel proteins from a variety of mechanoreceptors known in vertebrates. The overall expression patterns indicate the presence of the entire repertoire of neurons, glial cells and receptor proteins on the RNA level. This quantification suggests that the adipose fin contains considerable amounts of small nerve fibers with unmyelinated or slightly myelinated axons and most likely mechanoreceptive potential. The findings are consistent for both rainbow trout and maraena whitefish and support a previous hypothesis about the innervation and potential flow sensory function of the adipose fin. Moreover, our data suggest that the resection of the adipose fin has a stronger impact on the welfare of salmonid fish than previously assumed.

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Cell-Type-Specific Splicing of Piezo2 Regulates Mechanotransduction

Cited by 102 publications

References 50 publications

Profiling of how nociceptor neurons detect danger – new and old foes

Profiling of how nociceptor neurons detect danger – new and old foes

PIEZO1 functions as a potential oncogene by promoting cell proliferation and migration in gastric carcinogenesis

Gene Profiling in the Adipose Fin of Salmonid Fishes Supports Its Function as a Flow Sensor

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