CaMKII Potentiates Store-Operated Ca2+ Entry Through Enhancing STIM1 Aggregation and Interaction with Orai1
Background/Aims: Upon Ca2+ store depletion, stromal interaction molecule 1 (STIM1) oligomerizes, redistributes near plasmalemma to interact with Ca2+ selective channel-forming subunit (Orai1) and initiates store-operated Ca2+ entry (SOCE). Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a re...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Cell Physiol Biochem Press GmbH & Co KG
2018-04-01
|
| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | https://www.karger.com/Article/FullText/488835 |
| _version_ | 1818947277418397696 |
|---|---|
| author | Shu Li Jingyi Xue Zhipeng Sun Tiantian Liu Lane Zhang Limin Wang Hongjie You Zheng Fan Yuanyuan Zheng Dali Luo |
| author_facet | Shu Li Jingyi Xue Zhipeng Sun Tiantian Liu Lane Zhang Limin Wang Hongjie You Zheng Fan Yuanyuan Zheng Dali Luo |
| author_sort | Shu Li |
| collection | DOAJ |
| description | Background/Aims: Upon Ca2+ store depletion, stromal interaction molecule 1 (STIM1) oligomerizes, redistributes near plasmalemma to interact with Ca2+ selective channel-forming subunit (Orai1) and initiates store-operated Ca2+ entry (SOCE). Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a regulator of SOCE, but how CaMKII regulates SOCE remains obscure. Methods: Using Fura2, confocal microscopy, co-immunoprecipitation, specific blocker and overexpression/knockdown approaches, we evaluated STIM1 aggregation and its interaction with Orai1, and SOCE upon Ca2+ store depletion in thapsigargin (TG) treated HEK293 and HeLa cells. Results: Overexpression of CaMKIIδ enhanced TG-induced STIM1 co-localization and interaction with Orai1 as well as SOCE. In contrast, CaMKIIδ knockdown and a specific inhibitor of CaMKII suppressed them. In addition, overexpression or knockdown of CaMKIIδ in TG treated cells exhibited increased or reduced STIM1 clustering and plasmalemma redistribution, respectively. Conclusion: CaMKII up-regulates SOCE by increasing STIM1 aggregation and interaction with Orai1. This study provides an additional insight into SOCE regulation and a potential mechanism for CaMKII involvement in some pathological situations through crosstalk with SOCE. |
| first_indexed | 2024-12-20T08:28:21Z |
| format | Article |
| id | doaj.art-1b1b664d30634cf585e6bdd3b99584ae |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-20T08:28:21Z |
| publishDate | 2018-04-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-1b1b664d30634cf585e6bdd3b99584ae2022-12-21T19:46:46ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-04-014631042105410.1159/000488835488835CaMKII Potentiates Store-Operated Ca2+ Entry Through Enhancing STIM1 Aggregation and Interaction with Orai1Shu LiJingyi XueZhipeng SunTiantian LiuLane ZhangLimin WangHongjie YouZheng FanYuanyuan ZhengDali LuoBackground/Aims: Upon Ca2+ store depletion, stromal interaction molecule 1 (STIM1) oligomerizes, redistributes near plasmalemma to interact with Ca2+ selective channel-forming subunit (Orai1) and initiates store-operated Ca2+ entry (SOCE). Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a regulator of SOCE, but how CaMKII regulates SOCE remains obscure. Methods: Using Fura2, confocal microscopy, co-immunoprecipitation, specific blocker and overexpression/knockdown approaches, we evaluated STIM1 aggregation and its interaction with Orai1, and SOCE upon Ca2+ store depletion in thapsigargin (TG) treated HEK293 and HeLa cells. Results: Overexpression of CaMKIIδ enhanced TG-induced STIM1 co-localization and interaction with Orai1 as well as SOCE. In contrast, CaMKIIδ knockdown and a specific inhibitor of CaMKII suppressed them. In addition, overexpression or knockdown of CaMKIIδ in TG treated cells exhibited increased or reduced STIM1 clustering and plasmalemma redistribution, respectively. Conclusion: CaMKII up-regulates SOCE by increasing STIM1 aggregation and interaction with Orai1. This study provides an additional insight into SOCE regulation and a potential mechanism for CaMKII involvement in some pathological situations through crosstalk with SOCE.https://www.karger.com/Article/FullText/488835CaMKIIStore-operated Ca2+ entrySTIM1Orai1 |
| spellingShingle | Shu Li Jingyi Xue Zhipeng Sun Tiantian Liu Lane Zhang Limin Wang Hongjie You Zheng Fan Yuanyuan Zheng Dali Luo CaMKII Potentiates Store-Operated Ca2+ Entry Through Enhancing STIM1 Aggregation and Interaction with Orai1 Cellular Physiology and Biochemistry CaMKII Store-operated Ca2+ entry STIM1 Orai1 |
| title | CaMKII Potentiates Store-Operated Ca2+ Entry Through Enhancing STIM1 Aggregation and Interaction with Orai1 |
| title_full | CaMKII Potentiates Store-Operated Ca2+ Entry Through Enhancing STIM1 Aggregation and Interaction with Orai1 |
| title_fullStr | CaMKII Potentiates Store-Operated Ca2+ Entry Through Enhancing STIM1 Aggregation and Interaction with Orai1 |
| title_full_unstemmed | CaMKII Potentiates Store-Operated Ca2+ Entry Through Enhancing STIM1 Aggregation and Interaction with Orai1 |
| title_short | CaMKII Potentiates Store-Operated Ca2+ Entry Through Enhancing STIM1 Aggregation and Interaction with Orai1 |
| title_sort | camkii potentiates store operated ca2 entry through enhancing stim1 aggregation and interaction with orai1 |
| topic | CaMKII Store-operated Ca2+ entry STIM1 Orai1 |
| url | https://www.karger.com/Article/FullText/488835 |
| work_keys_str_mv | AT shuli camkiipotentiatesstoreoperatedca2entrythroughenhancingstim1aggregationandinteractionwithorai1 AT jingyixue camkiipotentiatesstoreoperatedca2entrythroughenhancingstim1aggregationandinteractionwithorai1 AT zhipengsun camkiipotentiatesstoreoperatedca2entrythroughenhancingstim1aggregationandinteractionwithorai1 AT tiantianliu camkiipotentiatesstoreoperatedca2entrythroughenhancingstim1aggregationandinteractionwithorai1 AT lanezhang camkiipotentiatesstoreoperatedca2entrythroughenhancingstim1aggregationandinteractionwithorai1 AT liminwang camkiipotentiatesstoreoperatedca2entrythroughenhancingstim1aggregationandinteractionwithorai1 AT hongjieyou camkiipotentiatesstoreoperatedca2entrythroughenhancingstim1aggregationandinteractionwithorai1 AT zhengfan camkiipotentiatesstoreoperatedca2entrythroughenhancingstim1aggregationandinteractionwithorai1 AT yuanyuanzheng camkiipotentiatesstoreoperatedca2entrythroughenhancingstim1aggregationandinteractionwithorai1 AT daliluo camkiipotentiatesstoreoperatedca2entrythroughenhancingstim1aggregationandinteractionwithorai1 |