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ndltd-OhioLink-oai-etd.ohiolink.edu-osu1148676549
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ndltd-OhioLink-oai-etd.ohiolink.edu-osu11486765492021-08-03T05:51:03Z Structure, function and regulation of TRP channels Wang, Chunbo Mammalian transient receptor potential (TRP) family is composed of 28 members and at least six of them are thermo-sensitive. TRPV3 is a thermosensitive member of the vallinoid subfamily (TRPV). The goal of this study is to understand the activation and regulation of TRPV3 and some other TRP channels. The data indicate that TRPV3 has many common properties shared with certain other TRP channels in activation and regulation. 2-amino epythoxydiphenyl borate (2APB) is widely used to inhibit inositol (1, 4, 5) trisphosphate receptors (IP3Rs) and store-operated calcium entry. In this study, 2APB is demonstrated to be a common agonist for TRPV1, -V2 and –V3, opposite to its inhibitory effect on TRPC6 and TRPM8. PMA treatment augments TRPV3 function via the activation of protein kinase C (PKC) phosphorylation. Disruption at five consensus PKC residues indicated that S688 is important for TRPV3 function. S688A had reduced response to 2APB and, when co-expressed with G protein-coupled receptors, S688A response to 2APB is rescued. TRPV3 function is also enhanced directly by arachidonic acid and other unsaturated fatty acids. The effect of the unsaturated fatty acids is not mediated by PKC phosphorylation or increasing the amount of TRPV3 proteins on the plasma membrane. Like other TRP channels including TRPV1 and TRPM2, TRPV3 is also spliced into different variants. Mouse TRPV3 is spliced into a shorter TRPV3 (TRPV3S) variant containing only the N-terminus and the first two transmembrane segments. TRPV3 and TRPV3S are expressed in the skin, brain, tongue, etc. TRPV3S is possibly not transported onto the plasma membrane by itself and TRPV3S itself has no channel function. TRPV3S interacts with TRPV3 and partially co-localizes with TRPV3 in HEK 293 cells. When co-expressed with TRPV3, TRPV3S increases the channel function of TRPV3. Camphor, an agonist for TRPV3, is demonstrated to be an agonist for TRPV1 and a partial agonist for TRPM8. In summary, the data indicate that there exist similarities and differences in the activation and regulation of TRPV3 and other TRP channels, indicative of common gating mechanisms and structural similarities among these TRP proteins. 2006-08-08 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1148676549 http://rave.ohiolink.edu/etdc/view?acc_num=osu1148676549 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
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| collection |
NDLTD
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| language |
English
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| sources |
NDLTD
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| author |
Wang, Chunbo
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| spellingShingle |
Wang, Chunbo
Structure, function and regulation of TRP channels
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| author_facet |
Wang, Chunbo
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| author_sort |
Wang, Chunbo
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| title |
Structure, function and regulation of TRP channels
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| title_short |
Structure, function and regulation of TRP channels
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| title_full |
Structure, function and regulation of TRP channels
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| title_fullStr |
Structure, function and regulation of TRP channels
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| title_full_unstemmed |
Structure, function and regulation of TRP channels
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| title_sort |
structure, function and regulation of trp channels
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| publisher |
The Ohio State University / OhioLINK
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| publishDate |
2006
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| url |
http://rave.ohiolink.edu/etdc/view?acc_num=osu1148676549
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AT wangchunbo structurefunctionandregulationoftrpchannels
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| _version_ |
1719426545266720768
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