Fibroblast growth factor homologous factor 1 (FHF1) is expressed in a subpopulation of calcitonin gene‐related peptide‐positive nociceptive neurons in the murine dorsal root ganglia

Abstract

Dorsal root ganglia (DRG) neurons exhibit a wide molecular heterogeneity in relation to the various sensory modalities (mechanoception, thermoception, nociception) that they subserve. Finding markers of subpopulations is an important step in understanding how these neurons convey specific information. We identified fibroblast growth factor homologous factor 1 (FHF1) in a search for markers of subpopulations of DRG neurons. FHFs constitute a family of four factors that share some structural properties with fibroblast growth factors (FGFs) but are functionally distinct. They are expressed in specific subsets of neurons and are involved in the modulation of sodium channel activity. The pattern of expression of FHF1 in the DRG was determined during development, in the adult and after axotomy. We show that in the adult, FHF1 is expressed in two populations, one composed of nociceptors and another in which no neurotrophic factor receptors were detected (panTrk-/c-Ret-). Interestingly, in the nociceptors, FHF1 expression was restricted to a subset of TrkA+/calcitonin gene-related peptide (CGRP)-positive neurons. Neurofilament 200 (NF-200) and peripherin labeling indicates that 70% of the FHF1-expressing neurons contribute to A-fibers and 30% to C-fibers. FHF1 interacts with the Na(v)1.9 sodium channel isoform, which is strongly expressed in cRet+/isolectin-B4 binding neurons, but we show that FHF1 is not expressed in the cRet+/IB4+ subclass and that it does not colocalize with Na(v)1.9. Our results argue strongly against the possibility that FHF1 has a modulatory effect on this channel in cRet+/IB4+ neurons, but FHF1 could play a role in a distinct subset of TrkA+/CGRP+ nociceptors.

NF-κB subunits are differentially distributed in cells of lumbar dorsal root ganglia in naïve and diabetic rats

“…Previous studies demonstrated that calcitonin gene-related peptide (CGRP) and isolectin B4 (IB4) are markers of Nerve Growth Factor (NGF) and Glial Cell Line-derived Neurotrophic Factor (GDNF)-sensitive small nociceptive neurons, respectively [12, 25]. In agreement with these reports, we observed that ~45% of small/ medium DRG neurons in naïve rats were positive for CGRP and IB4 (Fig.…”

FHF2 isoforms differentially regulate Nav1.6-mediated resurgent sodium currents in dorsal root ganglion neurons

“…One caveat with the FHFA antibody used is that it is not selective to the FHF2A isoform, but rather the antibody used targets the long-term inactivation particle which is highly conserved between all FHFAs. However, in adult DRG neurons, FHF4A is not expressed and FHF1A is downregulated in adulthood (27). FHF1A contains a nuclear localization signal that is functional in DRG neurons and targets the protein to the nucleus (27).…”

“…However, in adult DRG neurons, FHF4A is not expressed and FHF1A is downregulated in adulthood (27). FHF1A contains a nuclear localization signal that is functional in DRG neurons and targets the protein to the nucleus (27). In contrast, FHF2A nuclear localization signal is predicted to be inactive since staining is limited to the cell periphery and not detected in the nucleus in adult DRG neurons (48).…”

“…FHF interaction with VGSC can alter the biophysical properties of activation, inactivation and current density (19, 43). Adult DRG neurons can express a variety of FHF isoforms including FHF1, FHF2 and FHF4 (27, 35, 48, 63, 77). Each FHF gene can result in different isoforms through alternative splicing and promoter usage resulting in distinct N-terminal sequences (40).…”

Expression of nicotinic acetylcholine receptor subunit mRNA in mouse bladder afferent neurons

“…In mouse and rat sensory neurons, neurofilament proteins are expressed in large-diameter neurons with presumed high-conduction velocity while small neurons with presumed slow-conduction velocity express peripherin, a type III neuron-specific intermediate filament protein, without neurofilament coexpression (Troy et al, 1990;Goldstein et al, 1991;Hubert et al, 2008). Taking, on this basis, NF68-immunoreacitivity as a marker for A-fibre neurons, about a quarter of all lumbosacral bladder afferents is made up by fastconducting neurons expressing nAChRa3.…”