Regulation of InsP3 receptor activity by neuronal Ca2+-binding proteins.
Inositol 1,4,5-trisphosphate receptors (InsP(3)Rs) were recently demonstrated to be activated independently of InsP(3) by a family of calmodulin (CaM)-like neuronal Ca(2+)-binding proteins (CaBPs). We investigated the interaction of both naturally occurring long and short CaBP1 isoforms with InsP(3)...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2004
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| _version_ | 1797057649432330240 |
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| author | Kasri, N Holmes, A Bultynck, G Parys, J Bootman, MD Rietdorf, K Missiaen, L McDonald, F De Smedt, H Conway, S Holmes, AB Berridge, M Roderick, H |
| author_facet | Kasri, N Holmes, A Bultynck, G Parys, J Bootman, MD Rietdorf, K Missiaen, L McDonald, F De Smedt, H Conway, S Holmes, AB Berridge, M Roderick, H |
| author_sort | Kasri, N |
| collection | OXFORD |
| description | Inositol 1,4,5-trisphosphate receptors (InsP(3)Rs) were recently demonstrated to be activated independently of InsP(3) by a family of calmodulin (CaM)-like neuronal Ca(2+)-binding proteins (CaBPs). We investigated the interaction of both naturally occurring long and short CaBP1 isoforms with InsP(3)Rs, and their functional effects on InsP(3)R-evoked Ca(2+) signals. Using several experimental paradigms, including transient expression in COS cells, acute injection of recombinant protein into Xenopus oocytes and (45)Ca(2+) flux from permeabilised COS cells, we demonstrated that CaBPs decrease the sensitivity of InsP(3)-induced Ca(2+) release (IICR). In addition, we found a Ca(2+)-independent interaction between CaBP1 and the NH(2)-terminal 159 amino acids of the type 1 InsP(3)R. This interaction resulted in decreased InsP(3) binding to the receptor reminiscent of that observed for CaM. Unlike CaM, however, CaBPs do not inhibit ryanodine receptors, have a higher affinity for InsP(3)Rs and more potently inhibited IICR. We also show that phosphorylation of CaBP1 at a casein kinase 2 consensus site regulates its inhibition of IICR. Our data suggest that CaBPs are endogenous regulators of InsP(3)Rs tuning the sensitivity of cells to InsP(3). |
| first_indexed | 2024-03-06T19:39:23Z |
| format | Journal article |
| id | oxford-uuid:20255752-2a94-4216-ae19-4fc8bb208f82 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:39:23Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:20255752-2a94-4216-ae19-4fc8bb208f822022-03-26T11:25:50ZRegulation of InsP3 receptor activity by neuronal Ca2+-binding proteins.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:20255752-2a94-4216-ae19-4fc8bb208f82EnglishSymplectic Elements at Oxford2004Kasri, NHolmes, ABultynck, GParys, JBootman, MDRietdorf, KMissiaen, LMcDonald, FDe Smedt, HConway, SHolmes, ABBerridge, MRoderick, HInositol 1,4,5-trisphosphate receptors (InsP(3)Rs) were recently demonstrated to be activated independently of InsP(3) by a family of calmodulin (CaM)-like neuronal Ca(2+)-binding proteins (CaBPs). We investigated the interaction of both naturally occurring long and short CaBP1 isoforms with InsP(3)Rs, and their functional effects on InsP(3)R-evoked Ca(2+) signals. Using several experimental paradigms, including transient expression in COS cells, acute injection of recombinant protein into Xenopus oocytes and (45)Ca(2+) flux from permeabilised COS cells, we demonstrated that CaBPs decrease the sensitivity of InsP(3)-induced Ca(2+) release (IICR). In addition, we found a Ca(2+)-independent interaction between CaBP1 and the NH(2)-terminal 159 amino acids of the type 1 InsP(3)R. This interaction resulted in decreased InsP(3) binding to the receptor reminiscent of that observed for CaM. Unlike CaM, however, CaBPs do not inhibit ryanodine receptors, have a higher affinity for InsP(3)Rs and more potently inhibited IICR. We also show that phosphorylation of CaBP1 at a casein kinase 2 consensus site regulates its inhibition of IICR. Our data suggest that CaBPs are endogenous regulators of InsP(3)Rs tuning the sensitivity of cells to InsP(3). |
| spellingShingle | Kasri, N Holmes, A Bultynck, G Parys, J Bootman, MD Rietdorf, K Missiaen, L McDonald, F De Smedt, H Conway, S Holmes, AB Berridge, M Roderick, H Regulation of InsP3 receptor activity by neuronal Ca2+-binding proteins. |
| title | Regulation of InsP3 receptor activity by neuronal Ca2+-binding proteins. |
| title_full | Regulation of InsP3 receptor activity by neuronal Ca2+-binding proteins. |
| title_fullStr | Regulation of InsP3 receptor activity by neuronal Ca2+-binding proteins. |
| title_full_unstemmed | Regulation of InsP3 receptor activity by neuronal Ca2+-binding proteins. |
| title_short | Regulation of InsP3 receptor activity by neuronal Ca2+-binding proteins. |
| title_sort | regulation of insp3 receptor activity by neuronal ca2 binding proteins |
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