Dopamine negatively modulates the NCA ion channels in C. elegans.
The NALCN/NCA ion channel is a cation channel related to voltage-gated sodium and calcium channels. NALCN has been reported to be a sodium leak channel with a conserved role in establishing neuronal resting membrane potential, but its precise cellular role and regulation are unclear. The Caenorhabdi...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-10-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC5638609?pdf=render |
| _version_ | 1818598585030148096 |
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| author | Irini Topalidou Kirsten Cooper Laura Pereira Michael Ailion |
| author_facet | Irini Topalidou Kirsten Cooper Laura Pereira Michael Ailion |
| author_sort | Irini Topalidou |
| collection | DOAJ |
| description | The NALCN/NCA ion channel is a cation channel related to voltage-gated sodium and calcium channels. NALCN has been reported to be a sodium leak channel with a conserved role in establishing neuronal resting membrane potential, but its precise cellular role and regulation are unclear. The Caenorhabditis elegans orthologs of NALCN, NCA-1 and NCA-2, act in premotor interneurons to regulate motor circuit activity that sustains locomotion. Recently we found that NCA-1 and NCA-2 are activated by a signal transduction pathway acting downstream of the heterotrimeric G protein Gq and the small GTPase Rho. Through a forward genetic screen, here we identify the GPCR kinase GRK-2 as a new player affecting signaling through the Gq-Rho-NCA pathway. Using structure-function analysis, we find that the GPCR phosphorylation and membrane association domains of GRK-2 are required for its function. Genetic epistasis experiments suggest that GRK-2 acts on the D2-like dopamine receptor DOP-3 to inhibit Go signaling and positively modulate NCA-1 and NCA-2 activity. Through cell-specific rescuing experiments, we find that GRK-2 and DOP-3 act in premotor interneurons to modulate NCA channel function. Finally, we demonstrate that dopamine, through DOP-3, negatively regulates NCA activity. Thus, this study identifies a pathway by which dopamine modulates the activity of the NCA channels. |
| first_indexed | 2024-12-16T12:06:02Z |
| format | Article |
| id | doaj.art-eed701e442804a3d8f973bf895bd1de8 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-16T12:06:02Z |
| publishDate | 2017-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-eed701e442804a3d8f973bf895bd1de82022-12-21T22:32:19ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042017-10-011310e100703210.1371/journal.pgen.1007032Dopamine negatively modulates the NCA ion channels in C. elegans.Irini TopalidouKirsten CooperLaura PereiraMichael AilionThe NALCN/NCA ion channel is a cation channel related to voltage-gated sodium and calcium channels. NALCN has been reported to be a sodium leak channel with a conserved role in establishing neuronal resting membrane potential, but its precise cellular role and regulation are unclear. The Caenorhabditis elegans orthologs of NALCN, NCA-1 and NCA-2, act in premotor interneurons to regulate motor circuit activity that sustains locomotion. Recently we found that NCA-1 and NCA-2 are activated by a signal transduction pathway acting downstream of the heterotrimeric G protein Gq and the small GTPase Rho. Through a forward genetic screen, here we identify the GPCR kinase GRK-2 as a new player affecting signaling through the Gq-Rho-NCA pathway. Using structure-function analysis, we find that the GPCR phosphorylation and membrane association domains of GRK-2 are required for its function. Genetic epistasis experiments suggest that GRK-2 acts on the D2-like dopamine receptor DOP-3 to inhibit Go signaling and positively modulate NCA-1 and NCA-2 activity. Through cell-specific rescuing experiments, we find that GRK-2 and DOP-3 act in premotor interneurons to modulate NCA channel function. Finally, we demonstrate that dopamine, through DOP-3, negatively regulates NCA activity. Thus, this study identifies a pathway by which dopamine modulates the activity of the NCA channels.http://europepmc.org/articles/PMC5638609?pdf=render |
| spellingShingle | Irini Topalidou Kirsten Cooper Laura Pereira Michael Ailion Dopamine negatively modulates the NCA ion channels in C. elegans. PLoS Genetics |
| title | Dopamine negatively modulates the NCA ion channels in C. elegans. |
| title_full | Dopamine negatively modulates the NCA ion channels in C. elegans. |
| title_fullStr | Dopamine negatively modulates the NCA ion channels in C. elegans. |
| title_full_unstemmed | Dopamine negatively modulates the NCA ion channels in C. elegans. |
| title_short | Dopamine negatively modulates the NCA ion channels in C. elegans. |
| title_sort | dopamine negatively modulates the nca ion channels in c elegans |
| url | http://europepmc.org/articles/PMC5638609?pdf=render |
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