Piezo2 mechanosensitive ion channel is located to sensory neurons and non-neuronal cells in rat peripheral sensory pathway

AbstractPiezo2 mechanotransduction channel is a crucial mediator of sensory neurons for sensing and transducing touch, vibration, and proprioception. We here characterized Piezo2 expression and cell specificity in rat peripheral sensory pathway using a validated Piezo2 antibody. Immunohistochemistry using this antibody revealed Piezo2 expression in pan primary sensory neurons (PSNs) of dorsal rood ganglia (DRG) in naïve rats, which was actively transported along afferent axons to both central presynaptic terminals innervating the spinal dorsal horn (DH) and peripheral afferent terminals in skin. Piezo2 immunoreactivity (IR) was also detected in the postsynaptic neurons of the DH and in the motor neurons of the ventral horn, but not in spinal GFAP- and Iba1-positive glia. Notably, Piezo2-IR was clearly identified in peripheral non-neuronal cells, including perineuronal glia, Schwann cells in the sciatic nerve and surrounding cutaneous afferent endings, as well as in skin epidermal Merkel cells and melanocytes. Immunoblots showed increased Piezo2 in DRG ipsilateral to plantar injection of complete Freund’s adjuvant (CFA), and immunostaining revealed increased Piezo2-IR intensity in the DH ipsilateral to CFA injection. This elevation of DH Piezo2-IR was also evident in various neuropathic pain models and monosodium iodoacetate (MIA) knee osteoarthritis (OA) pain model, compared to controls. We conclude that 1) the pan neuronal profile of Piezo2 expression suggests that Piezo2 may function extend beyond simply touch/proprioception mediated by large-sized low-threshold mechanosensitive PSNs, 2) Piezo2 may have functional roles involving sensory processing in spinal cord, Schwann cells, and skin melanocytes, and 3) aberrant Piezo2 expression may contribute pain pathogenesis.

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Acetylated tubulin is essential for touch sensation in mice

eLife ◽

10.7554/elife.20813 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 41

Author(s):

Shane J Morley ◽

Yanmei Qi ◽

Loredana Iovino ◽

Laura Andolfi ◽

Da Guo ◽

...

Keyword(s):

Ion Channel ◽

Sensory Neurons ◽

Mechanical Energy ◽

Mechanical Stimuli ◽

Acetylated Tubulin ◽

Fundamental Level ◽

Tubulin Acetylation ◽

Channel Opening ◽

Mechanosensitive Ion Channel ◽

Touch Sensation

At its most fundamental level, touch sensation requires the translation of mechanical energy into mechanosensitive ion channel opening, thereby generating electro-chemical signals. Our understanding of this process, especially how the cytoskeleton influences it, remains unknown. Here we demonstrate that mice lacking the α-tubulin acetyltransferase Atat1 in sensory neurons display profound deficits in their ability to detect mechanical stimuli. We show that all cutaneous afferent subtypes, including nociceptors have strongly reduced mechanosensitivity upon Atat1 deletion, and that consequently, mice are largely insensitive to mechanical touch and pain. We establish that this broad loss of mechanosensitivity is dependent upon the acetyltransferase activity of Atat1, which when absent leads to a decrease in cellular elasticity. By mimicking α-tubulin acetylation genetically, we show both cellular rigidity and mechanosensitivity can be restored in Atat1 deficient sensory neurons. Hence, our results indicate that by influencing cellular stiffness, α-tubulin acetylation sets the force required for touch.

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Target-induced neurogenesis in the leech CNS involves efferent projections to the target

Development ◽

10.1242/dev.121.2.359 ◽

1995 ◽

Vol 121 (2) ◽

pp. 359-369 ◽

Cited By ~ 1

Author(s):

T. Becker ◽

A.J. Berliner ◽

M.N. Nitabach ◽

W.B. Gan ◽

E.R. Macagno

Keyword(s):

Sensory Neurons ◽

Male Genitalia ◽

Critical Period ◽

Neuronal Cells ◽

Sexual Organ ◽

Central Neurons ◽

Efferent Projections ◽

Male Organ ◽

Peripheral Sensory ◽

Inductive Signal

During a critical period in leech embryogenesis, the sex nerves that connect the 5th and 6th midbody ganglia (MG5 and MG6) to the primordium of the male sexual organ carry a spatially localized signal that induces the birth of several hundred neurons specific to these ganglia. We examined particular cellular elements (afferents, efferents, non-neuronal components) within these nerves as potential conveyors of the inductive signal. We show that axons of peripheral sensory neurons in the male genitalia travel along the sex nerves and into MG5 and MG6, but reach the CNS after the critical period has elapsed and cannot, therefore, be involved in the induction. Of the six sex nerves, four contain non-neuronal cells that span the entire distance between the male genitalia and the sex ganglia. However, when male genitalia were transplanted to ectopic locations close to MG6, induction occurred frequently but only in MG6, mediated by ectopic nerves that do not contain these cells. Thus, non-neuronal cells specific to the normal sex nerves are not necessary for induction. In addition, dye injections into the target during the critical period failed to reveal migrating cells in the sex nerves that could convey the inductive signal to the CNS. Finally, we show that 11 pairs of central neurons in each ganglion project to the male organ early during the critical period. In the adult, at least 3 additional pairs of neurons in MG6 also innervate this target. We conclude that the only components of the sex nerves that connect the sex ganglia to the target during the critical period that could be associated with induced central mitogenesis are the axons of central neurons that innervate the male genitalia.

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Peripheral sensory neurons and non-neuronal cells express functional Piezo1 that is activated in peripheral nerve injury-induced neuropathic pain

10.1101/2021.10.05.463243 ◽

2021 ◽

Author(s):

Seung Min Shin ◽

Brandon Itson-Zoske ◽

Fan Fan ◽

Cheryl L. Stucky ◽

Quinn H. Hogan ◽

...

Keyword(s):

Neuropathic Pain ◽

Sciatic Nerve ◽

Peripheral Nerve ◽

Schwann Cells ◽

Nerve Injury ◽

Sensory Neurons ◽

Peripheral Nerve Injury ◽

Neuronal Cells ◽

Satellite Glial Cells ◽

Peripheral Sensory

AbstractHere, we present evidence showing Piezo1 expression in the primary sensory neurons (PSNs) and non-neuronal cells of rat peripheral nervous system. Using a knockdown/knockout validated antibody, we detected Piezo1 immunoreactivity (IR) in ∼80% of PSNs of rat dorsal root ganglia (DRG) with higher IR density in the small- and medium-sized neurons, and within axons extending to both central presynaptic terminals innervating to the spinal dorsal horn and peripheral cutaneous sensory terminals in the skin. Piezo-IR was clearly identified in DRG perineuronal glia, including satellite glial cells (SGCs) and non-myelinating Schwann cells; in sciatic nerve Schwann cells surrounding the axons and cutaneous afferent endings; and in skin epidermal Merkel cells and melanocytes. Neuronal and non-neuronal Piezo1 channels were functional, since various cells (dissociated PSNs and SGCs from DRGs, isolated Schwann cells, and primary human melanocytes) exhibited a robust response to Piezo1 agonist Yoda1 by an increase of intracellular Ca2+ concentration ([Ca2+]i). These responses were abolished by Piezo1 antagonist GsMTx4. Immunoblots showed elevated Piezo1 protein in DRG proximal to peripheral nerve injury-induced painful neuropathy, while PSNs and SGCs from rats with neuropathic pain showed greater Yuda1-evoked elevation of [Ca2+]i and an increased frequency of cells responding to Yoda1, compared to controls. Ipsilateral sciatic nerve application of GsMTx4 alleviated mechanical hypersensitivity following nerve injury. Overall, our data show that Piezo1 is widely expressed by the neuronal and non-neuronal cells in the peripheral sensory pathways and that painful nerve injury is associated with activation of Piezo1 in PSNs and peripheral glia cells.

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