TRPM7 residue S1269 mediates cAMP dependence of Ca2+ influx.
The nonspecific divalent cation channel TRPM7 (transient receptor potential-melastatin-like 7) is involved in many Ca2+ and Mg2+-dependent cellular processes, including survival, proliferation and migration. TRPM7 expression predicts metastasis and recurrence in breast cancer and several other cance...
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Online Access: | https://doi.org/10.1371/journal.pone.0209563 |
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doaj-d2306007c79e4a6089aca46e52bfe9462021-03-03T20:59:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01141e020956310.1371/journal.pone.0209563TRPM7 residue S1269 mediates cAMP dependence of Ca2+ influx.Jorrit BroertjesJeffrey KlarenbeekYasmin HabaniMichiel LangeslagKees JalinkThe nonspecific divalent cation channel TRPM7 (transient receptor potential-melastatin-like 7) is involved in many Ca2+ and Mg2+-dependent cellular processes, including survival, proliferation and migration. TRPM7 expression predicts metastasis and recurrence in breast cancer and several other cancers. In cultured cells, it can induce an invasive phenotype by promoting Ca2+-mediated epithelial-mesenchymal transition. We previously showed that in neuroblastoma cells that overexpress TRPM7 moderately, stimulation with Ca2+-mobilizing agonists leads to a characteristic sustained influx of Ca2+. Here we report that sustained influx through TRPM7 is abruptly abrogated by elevating intracellular levels of cyclic adenosine monophosphate (cAMP). Using pharmacological inhibitors and overexpression studies we show that this blockage is mediated by the cAMP effector Protein Kinase A (PKA). Mutational analysis demonstrates that the Serine residue S1269, which is present proximal to the coiled-coil domain within the protein c-terminus, is responsible for sensitivity to cAMP.https://doi.org/10.1371/journal.pone.0209563 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jorrit Broertjes Jeffrey Klarenbeek Yasmin Habani Michiel Langeslag Kees Jalink |
spellingShingle |
Jorrit Broertjes Jeffrey Klarenbeek Yasmin Habani Michiel Langeslag Kees Jalink TRPM7 residue S1269 mediates cAMP dependence of Ca2+ influx. PLoS ONE |
author_facet |
Jorrit Broertjes Jeffrey Klarenbeek Yasmin Habani Michiel Langeslag Kees Jalink |
author_sort |
Jorrit Broertjes |
title |
TRPM7 residue S1269 mediates cAMP dependence of Ca2+ influx. |
title_short |
TRPM7 residue S1269 mediates cAMP dependence of Ca2+ influx. |
title_full |
TRPM7 residue S1269 mediates cAMP dependence of Ca2+ influx. |
title_fullStr |
TRPM7 residue S1269 mediates cAMP dependence of Ca2+ influx. |
title_full_unstemmed |
TRPM7 residue S1269 mediates cAMP dependence of Ca2+ influx. |
title_sort |
trpm7 residue s1269 mediates camp dependence of ca2+ influx. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2019-01-01 |
description |
The nonspecific divalent cation channel TRPM7 (transient receptor potential-melastatin-like 7) is involved in many Ca2+ and Mg2+-dependent cellular processes, including survival, proliferation and migration. TRPM7 expression predicts metastasis and recurrence in breast cancer and several other cancers. In cultured cells, it can induce an invasive phenotype by promoting Ca2+-mediated epithelial-mesenchymal transition. We previously showed that in neuroblastoma cells that overexpress TRPM7 moderately, stimulation with Ca2+-mobilizing agonists leads to a characteristic sustained influx of Ca2+. Here we report that sustained influx through TRPM7 is abruptly abrogated by elevating intracellular levels of cyclic adenosine monophosphate (cAMP). Using pharmacological inhibitors and overexpression studies we show that this blockage is mediated by the cAMP effector Protein Kinase A (PKA). Mutational analysis demonstrates that the Serine residue S1269, which is present proximal to the coiled-coil domain within the protein c-terminus, is responsible for sensitivity to cAMP. |
url |
https://doi.org/10.1371/journal.pone.0209563 |
work_keys_str_mv |
AT jorritbroertjes trpm7residues1269mediatescampdependenceofca2influx AT jeffreyklarenbeek trpm7residues1269mediatescampdependenceofca2influx AT yasminhabani trpm7residues1269mediatescampdependenceofca2influx AT michiellangeslag trpm7residues1269mediatescampdependenceofca2influx AT keesjalink trpm7residues1269mediatescampdependenceofca2influx |
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