Negative Regulation of the Creatine Transporter SLC6A8 by SPAK and OSR1
Background/Aims: Transport regulation involves several kinases including SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1), which are under control of WNK (with-no-K[Lys]) kinases. The present study explored whether SPAK and/or OSR1 participate in the re...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Karger Publishers
2014-12-01
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| Series: | Kidney & Blood Pressure Research |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/368465 |
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| author | Myriam Fezai Bernat Elvira Jose Borras Mossadok Ben-Attia Zohreh Hoseinzadeh Florian Lang |
| author_facet | Myriam Fezai Bernat Elvira Jose Borras Mossadok Ben-Attia Zohreh Hoseinzadeh Florian Lang |
| author_sort | Myriam Fezai |
| collection | DOAJ |
| description | Background/Aims: Transport regulation involves several kinases including SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1), which are under control of WNK (with-no-K[Lys]) kinases. The present study explored whether SPAK and/or OSR1 participate in the regulation of the creatine transporter CreaT (SLC6A8), which accomplishes Na+ coupled cellular uptake of creatine in several tissues including kidney, intestine, heart, skeletal muscle and brain. Methods: cRNA encoding SLC6A8 was injected into Xenopus laevis oocytes with or without additional injection of cRNA encoding wild-type SPAK, constitutively active T233ESPAK, WNK insensitive T233ASPAK, catalytically inactive D212ASPAK, wild-type OSR1, constitutively active T185EOSR1, WNK insensitive T185AOSR1 and catalytically inactive D164AOSR1. Transporter activity was determined from creatine (1 mM) induced current utilizing dual electrode voltage clamp. Results: Coexpression of wild-type SPAK and of T233ESPAK, but not of T233ASPAK or of D212ASPAK was followed by a significant decrease of creatine induced current in SLC6A8 expressing oocytes. Coexpression of SPAK significantly decreased maximal transport rate. Coexpression of wild-type OSR1, T185EOSR1 and T185AOSR1 but not of D164AOSR1 significantly negatively regulated SLC6A8 activity. OSR1 again decreased significantly maximal transport rate. Conclusions: Both, SPAK and OSR1, are negative regulators of the creatine transporter SLC6A8. |
| first_indexed | 2024-12-12T09:41:05Z |
| format | Article |
| id | doaj.art-f0c2eeae740f4a388178d2f8dc6270b3 |
| institution | Directory Open Access Journal |
| issn | 1420-4096 1423-0143 |
| language | English |
| last_indexed | 2024-12-12T09:41:05Z |
| publishDate | 2014-12-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Kidney & Blood Pressure Research |
| spelling | doaj.art-f0c2eeae740f4a388178d2f8dc6270b32022-12-22T00:28:34ZengKarger PublishersKidney & Blood Pressure Research1420-40961423-01432014-12-0139654655410.1159/000368465368465Negative Regulation of the Creatine Transporter SLC6A8 by SPAK and OSR1Myriam FezaiBernat ElviraJose BorrasMossadok Ben-AttiaZohreh HoseinzadehFlorian LangBackground/Aims: Transport regulation involves several kinases including SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1), which are under control of WNK (with-no-K[Lys]) kinases. The present study explored whether SPAK and/or OSR1 participate in the regulation of the creatine transporter CreaT (SLC6A8), which accomplishes Na+ coupled cellular uptake of creatine in several tissues including kidney, intestine, heart, skeletal muscle and brain. Methods: cRNA encoding SLC6A8 was injected into Xenopus laevis oocytes with or without additional injection of cRNA encoding wild-type SPAK, constitutively active T233ESPAK, WNK insensitive T233ASPAK, catalytically inactive D212ASPAK, wild-type OSR1, constitutively active T185EOSR1, WNK insensitive T185AOSR1 and catalytically inactive D164AOSR1. Transporter activity was determined from creatine (1 mM) induced current utilizing dual electrode voltage clamp. Results: Coexpression of wild-type SPAK and of T233ESPAK, but not of T233ASPAK or of D212ASPAK was followed by a significant decrease of creatine induced current in SLC6A8 expressing oocytes. Coexpression of SPAK significantly decreased maximal transport rate. Coexpression of wild-type OSR1, T185EOSR1 and T185AOSR1 but not of D164AOSR1 significantly negatively regulated SLC6A8 activity. OSR1 again decreased significantly maximal transport rate. Conclusions: Both, SPAK and OSR1, are negative regulators of the creatine transporter SLC6A8.http://www.karger.com/Article/FullText/368465Oxidative stress-responsive kinase 1CreaTSPS1-related proline/alanine-rich kinaseWNK |
| spellingShingle | Myriam Fezai Bernat Elvira Jose Borras Mossadok Ben-Attia Zohreh Hoseinzadeh Florian Lang Negative Regulation of the Creatine Transporter SLC6A8 by SPAK and OSR1 Kidney & Blood Pressure Research Oxidative stress-responsive kinase 1 CreaT SPS1-related proline/alanine-rich kinase WNK |
| title | Negative Regulation of the Creatine Transporter SLC6A8 by SPAK and OSR1 |
| title_full | Negative Regulation of the Creatine Transporter SLC6A8 by SPAK and OSR1 |
| title_fullStr | Negative Regulation of the Creatine Transporter SLC6A8 by SPAK and OSR1 |
| title_full_unstemmed | Negative Regulation of the Creatine Transporter SLC6A8 by SPAK and OSR1 |
| title_short | Negative Regulation of the Creatine Transporter SLC6A8 by SPAK and OSR1 |
| title_sort | negative regulation of the creatine transporter slc6a8 by spak and osr1 |
| topic | Oxidative stress-responsive kinase 1 CreaT SPS1-related proline/alanine-rich kinase WNK |
| url | http://www.karger.com/Article/FullText/368465 |
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