Involvement of advillin in somatosensory neuron subtype-specific axon regeneration and neuropathic pain

Abstract

SignificanceAn estimated 20 million people in the United States have chronic neuropathic pain, but current analgesics are nonspecific or insufficiently effective. Here we show that advillin, a sensory neuron-specific protein, modulates axonal regeneration of a specific subset of pain-sensing afferent neurons (nociceptors) that binds with isolectin B4 and neuropathic pain. In addition, we identify the cell behavior of advillin shed-off from the growth cone in the context of axonal regeneration and thus detected advillin protein in the cerebrospinal fluid in mice with painful peripheral neuropathy. Advillin is a potential biosignature to diagnose the lesion cause of neuropathic pain associated with isolectin B4+ nociceptors.

Advillin is a tuft cell marker in the mouse alimentary tract

“…1 f). Dorsal root ganglia harbor sensory neurons that are known to express Avil , but not Vil (Chuang et al 2018 ). In our hand, the anti-villin antibodies did not show cross-reactivity with mouse advillin, because they failed to label dorsal root ganglia neurons (Fig.…”

“…In mice, a comparison of the transcriptional profiles of small intestinal TRPM5-positive tuft cells with that of other enterocytes revealed that villin was expressed equally strong in both cell populations, while advillin expression was restricted to tuft cells (Bezençon et al 2008 ). To be sure that our immunohistochemical tools had an adequate specificity, we stained sections containing taste cells, which express both, villin and advillin, and dorsal root ganglia that are known to express advillin but not villin (Chuang et al 2018 ). We found similar staining patterns for villin and advillin in taste cells, however many dorsal root ganglia neurons stained for advillin, but not for villin, thus ruling out advillin cross-reactivity of the anti-villin antibody.…”

“…Originally, advillin expression was considered to be largely restricted to sensory neurons (Chuang et al 2018 ). We were able to show by IHC that advillin was present in sensory neurons of dorsal root ganglia, while villin was not.…”

“…Advillin, initially named p92 (Marks et al 1998 ), is a member of the gelsolin/villin superfamily of actin regulatory proteins. Advillin expression pattern analysis suggested that it is expressed almost exclusively by sensory neurons during development and in adulthood (Chuang et al 2018 ; Hasegawa et al 2007 ). Recently, Avil promoter-driven expression of either Egfp or Cre -recombinase extended the Avil expression pattern to diverse sets of central and peripheral neurons, including all neural crest-derived ganglia (Hunter et al 2018 ).…”

Peer Review #1 of "A transcriptomic study of probenecid on injured spinal cords in mice (v0.1)"

“…Among these signal pathways, some are known to be related to SCI, such as CAMs (Brook et al 2000;Zhang et al 2008), ECM-receptor interaction (Zhou et al 2017 Manuscript to be reviewed pathway (Li et al 2019a;Li et al 2019b;Zhang et al 2017) and focal adhesion (Chuang et al 2018;Graham et al 2016;Hao et al 2018).…”