TRPC4 in Rat Dorsal Root Ganglion Neurons Is Increased after Nerve Injury and Is Necessary for Neurite Outgrowth

Wu, Dongsheng; Huang, Wenlong; Richardson, P. M.; Priestley, John V.; Liu, Min

doi:10.1074/jbc.m703177200

Cited by 78 publications

(71 citation statements)

References 50 publications

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“…2B). We also isolated mRNA from lysates of dissociated DRG neurons and detected TRPC5 transcripts (24). TRPC5 also is present in human tissues, and immunolabeling demonstrated that TRPC5 is expressed in intraepithelial nerve endings within the human skin (Fig.…”

Section: Trpc5mentioning

confidence: 99%

Transient receptor potential cation channel, subfamily C, member 5 (TRPC5) is a cold-transducer in the peripheral nervous system

Zimmermann

Lennerz

Hein³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

202

168

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Detection and adaptation to cold temperature is crucial to survival. Cold sensing in the innocuous range of cold (>10-15°C) in the mammalian peripheral nervous system is thought to rely primarily on transient receptor potential (TRP) ion channels, most notably the menthol receptor, TRPM8. Here we report that TRP cation channel, subfamily C member 5 (TRPC5), but not TRPC1/TRPC5 heteromeric channels, are highly cold sensitive in the temperature range 37-25°C. We found that TRPC5 is present in mouse and human sensory neurons of dorsal root ganglia, a substantial number of peripheral nerves including intraepithelial endings, and in the dorsal lamina of the spinal cord that receives sensory input from the skin, consistent with a potential TRPC5 function as an innocuous cold transducer in nociceptive and thermosensory nerve endings. Although deletion of TRPC5 in 129S1/SvImJ mice resulted in no temperature-sensitive behavioral changes, TRPM8 and/or other menthol-sensitive channels appear to underpin a much larger component of noxious cold sensing after TRPC5 deletion and a shift in mechanosensitive C-fiber subtypes. These findings demonstrate that highly cold-sensitive TRPC5 channels are a molecular component for detection and regional adaptation to cold temperatures in the peripheral nervous system that is distinct from noxious cold sensing.pain | single-fiber | thermo-transient receptor potential | nociception | temperature sensing N ociceptors and thermoreceptive neurons, such as cold and heat receptors, innervate the skin and deep tissues. The cell bodies of sensory nerve endings are clustered in ganglia located in the vertebral column and cranium. Their projections extend to the skin where they arborize in terminals embedded between keratinocytes. Although nociceptors are polymodal and respond to stimuli (cold, heat, pressure, and noxious chemicals) that are capable of producing tissue damage and pain (1), cold receptors are unimodal and specialized to detect cool and cold temperatures (2). Transient receptor potential (TRP) ion channels are principal transducers of thermal stimuli that depolarize nerve terminals to the action potential threshold. Action potentials then relay the sensory information to integrative centers in the spinal cord and brain.All proteins are temperature sensitive, but most ion channels exhibit two-to threefold increases in gating with a 10°C change in temperature (Q 10 = 2-3). Certain ion channels exhibit dramatic temperature sensitivity in gating over physiologically relevant ranges (Q 10 = 10-30). Mammalian ion channels with such high Q 10 values include particular two-pore K + channels (3), the voltage-gated proton channel (4), transient receptor potential cation channel subfamily V members 1-3 (TRPV1-3) (5-7), transient receptor potential menthol receptor 8 (TRPM8) (8), and in some reports, TRP cation channel subfamily A member 1 (TRPA1) (9, 10). There is no a priori requirement for cold encoding by high Q 10 channels-action potential firing rates are affected perforce by temperature,...

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Section: Trpc5mentioning

confidence: 99%

Transient receptor potential cation channel, subfamily C, member 5 (TRPC5) is a cold-transducer in the peripheral nervous system

Zimmermann

Lennerz

Hein³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

202

168

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“…Given the exclusive expression pattern of all three Mrg receptors in DRG, we tested species-specific alterations of receptor endocytosis in a second DRG-like cell line. ND-C cells have been established as a model system to analyze the pharmacological properties of DRG-specific proteins on the cellular level (Wood et al, 1990;Tang et al, 1994;Wu et al, 2008); thus, we have chosen these cells to further determine species-specific differences in Mrg receptor endocytosis. Stimulation of ND-C cells transfected with the respective cDNAs coding for Ex-tagged Mrg receptors confirmed that both rodent MrgC receptors are prone to agonistpromoted endocytosis either induced by BAM8-22 or ␥ 2 -MSH and that hMrgX1s resist BAM8-22-promoted endocytosis (Fig.…”

Section: Calcium Signaling and Receptor Endocytosis In Hek293 Cells Smentioning

confidence: 99%

Sensory Neuron-Specific Mas-Related Gene-X1 Receptors Resist Agonist-Promoted Endocytosis

Solinski

Boekhoff²,

Bouvier³

et al. 2010

Mol Pharmacol

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Human sensory neuron-specific mas-related gene X1 receptors (hMrgX1s) belong to the superfamily of G protein-coupled receptors (GPCRs), bind cleavage products of pro-enkephalin with high affinity, and have been suggested to participate in pain sensation. Murine or rat MrgC receptors exhibit high similarities with hMrgX1 in terms of expression pattern, sequence homology, and binding profile. Therefore, rodents have been used as an in vivo model to explore the physiological functions and pharmacodynamics of the hMrgX1. Agonist-promoted receptor endocytosis significantly affects the pharmacodynamics of a GPCR but is not yet investigated for hMrgX1. Therefore, we analyzed the effects of prolonged agonist exposure on cell surface protein levels of hMrgX1 and murine or rat MrgC in human embryonic kidney 293, Cos, F11, and ND-C cells. We observed that hMrgX1 are resistant and both MrgC are prone to agonist-promoted receptor endocytosis. In Cos cells, coexpression of ␤-arrestins strongly enhanced endocytosis of murine MrgC but did not alter cell surface expression of hMrgX1 receptors. These data define the hMrgX1 as one of the few members within the superfamily of GPCRs whose signaling is not regulated by agonist-promoted endocytosis and reveal species-specific differences in the regulation of Mrg receptor signaling. Given the importance of receptor endocytosis for the pharmacodynamics of a given ligand, our results may have a strong impact on the development of future drugs that suppose to control pain in humans but were tested in rodents.

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“…heart, brain, sperm TRPC3 1/1.5-1.6 DAG, InsP 3 R Brain, placenta, heart, muscle Hippocampal neurons↑ [14] TRPC4 1/7 Receptor-operated Brain, endothelia, adrenal gland, DRG neurons↑ [26] Store-operated? retina, testis Hippocampal neurons↓ [18] TRPC5 1/9-9.5 Receptor-operated Brain PC12 cells↓ [27] Store-operated?…”

Section: Discussionmentioning

confidence: 99%

“…TRPC4, which belongs to the same subfamily as TRPC5, inhibits dendritic growth in hippocampal neurons [18] . However, suppression of TRPC4 by a specifi c siRNA or shRNA signifi cantly reduces the length of neurites in cultured dorsal root ganglion neurons [26] . Meanwhile, opposing regulatory effects of TRPC1 and TRPC5 on neurite outgrowth in PC12 cells have been reported [27] .…”

Section: Developmentmentioning

confidence: 99%

Ca2+ signaling initiated by canonical transient receptor potential channels in dendritic development

Feng

et al. 2015

Neurosci. Bull.

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TRPC4 in Rat Dorsal Root Ganglion Neurons Is Increased after Nerve Injury and Is Necessary for Neurite Outgrowth

Cited by 78 publications

References 50 publications

Transient receptor potential cation channel, subfamily C, member 5 (TRPC5) is a cold-transducer in the peripheral nervous system

Transient receptor potential cation channel, subfamily C, member 5 (TRPC5) is a cold-transducer in the peripheral nervous system

Sensory Neuron-Specific Mas-Related Gene-X1 Receptors Resist Agonist-Promoted Endocytosis

Ca2+ signaling initiated by canonical transient receptor potential channels in dendritic development

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