title: A functional nuclear localization sequence in the C. elegans TRPV channel OCR-2.
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 Ca(v)1.2 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.
authors.affiliation: Department of Biological Sciences, State University of New York at Buffalo, Buffalo, New York, United States of America.
authors.forename: Meredith J
authors.initials: MJ
authors.lastname: Ezak
authors.forename: Denise M
authors.initials: DM
authors.lastname: Ferkey
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005786:Gene Expression Regulation; D007473:Ion Channels / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D019913:Nuclear Localization Signals / Q000737:chemistry / Q000378:metabolism*; D018035:Receptors, Odorant / Q000378:metabolism; D050916:TRPV Cation Channels
chemical_list: D029742:Caenorhabditis elegans Proteins; D007473:Ion Channels; D009419:Nerve Tissue Proteins; D019913:Nuclear Localization Signals; C464590:OCR-2 protein, C elegans; C109039:ODR-10 protein, C elegans; D018035:Receptors, Odorant; D050916:TRPV Cation Channels