Abstract
The ability to modulate gene expression in response to sensory experience is critical to the normal development and function of the nervous system. Calcium is a key activator of the signal transduction cascades that mediate the process of translating a cellular stimulus into transcriptional changes. With the recent discovery that the mammalian Cav1.2 calcium channel can be cleaved, enter the nucleus and act as a transcription factor to control neuronal gene expression, a more direct role for the calcium channels themselves in regulating transcription has begun to be appreciated. Here we report the identification of a nuclear localization sequence (NLS) in the C. elegans transient receptor potential vanilloid (TRPV) cation channel OCR-2. TRPV channels have previously been implicated in transcriptional regulation of neuronal genes in the nematode, although the precise mechanism remains unclear. We show that the NLS in OCR-2 is functional, being able to direct nuclear accumulation of a synthetic cargo protein as well as the carboxy-terminal cytosolic tail of OCR-2 where it is endogenously found. Furthermore, we discovered that a carboxy-terminal portion of the full-length channel can localize to the nucleus of neuronal cells. These results suggest that the OCR-2 TRPV cation channel may have a direct nuclear function in neuronal cells that was not previously appreciated.
Highlights
The transient receptor potential (TRP) family of ion channels can be found in all eukaryotes from yeast to mammals [1,2]
While they are best known for their thermosensitivity, with 4 of the 6 members being activated by heat, TRP vanilloid family (TRPV) are broadly involved in nociception and are activated by a variety of physiologically important cues including osmotic cell swelling, noxious chemicals, analgesic compounds, inflammatory cytokines, calcium store depletion and polyunsaturated fatty acids (PUFAs) [1,3,4]
We report the discovery of a bipartite nuclear localization sequence (NLS) in the cytoplasmic carboxy-terminus of the C. elegans TRPV cation channel OCR-2
Summary
The transient receptor potential (TRP) family of ion channels can be found in all eukaryotes from yeast to mammals [1,2]. Mammalian TRP vanilloid family (TRPV) channels range from modestly to highly calcium permeable and contain 3–5 cytoplasmic amino-terminal ankyrin repeats as well as a long, unconserved carboxy-terminal cytoplasmic tail [1,5]. TRPVs are widely expressed in mammals, but most thoroughly studied in sensory neurons [4]. While they are best known for their thermosensitivity, with 4 of the 6 members being activated by heat, TRPVs are broadly involved in nociception and are activated by a variety of physiologically important cues including osmotic cell swelling, noxious chemicals, analgesic compounds, inflammatory cytokines, calcium store depletion and polyunsaturated fatty acids (PUFAs) [1,3,4]. Most TRPVs are polymodally activated, allowing them to integrate signals from multiple cellular pathways [3]
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