IQGAP1 activates PLC‐δ1 by direct binding and moving along microtubule with DLC‐1 to cell surface
Abstract Phospholipase C (PLC)‐δ1, activated by p122RhoGTPase‐activating protein (GAP)/deleted in liver cancer‐1 (p122RhoGAP/DLC‐1), contributes to the coronary spastic angina (CSA) pathogenesis. The present study aims to further investigate the p122RhoGAP/DLC‐1 protein. We examined molecules assist...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-08-01
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| Series: | FASEB BioAdvances |
| Subjects: | |
| Online Access: | https://doi.org/10.1096/fba.2019-00020 |
| _version_ | 1818825695153881088 |
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| author | Makoto Tanaka Tomohiro Osanai Yoshimi Homma Kenji Hanada Ken Okumura Hirofumi Tomita |
| author_facet | Makoto Tanaka Tomohiro Osanai Yoshimi Homma Kenji Hanada Ken Okumura Hirofumi Tomita |
| author_sort | Makoto Tanaka |
| collection | DOAJ |
| description | Abstract Phospholipase C (PLC)‐δ1, activated by p122RhoGTPase‐activating protein (GAP)/deleted in liver cancer‐1 (p122RhoGAP/DLC‐1), contributes to the coronary spastic angina (CSA) pathogenesis. The present study aims to further investigate the p122RhoGAP/DLC‐1 protein. We examined molecules assisting this protein and identified a scaffold protein—IQ motif‐containing GTPase‐activating protein 1 (IQGAP1). IQGAP1‐C binds to the steroidogenic acute regulatory‐related lipid transfer (START) domain of p122RhoGAP/DLC‐1, and PLC‐δ1 binds to IQGAP1‐N, forming a complex. In fluorescence microscopy, small dots of PLC‐δ1 created fine linear arrays like microtubules, and IQGAP1 and p122RhoGAP/DLC‐1 were colocated in the cytoplasm with PLC‐δ1. Ionomycin induced the raft recruitment of the PLC‐δ1, IQGAP1, and p122RhoGAP/DLC‐1 complex by translocation to the plasma membrane (PM), indicating the movement of this complex is along microtubules with the motor protein kinesin. Moreover, the IQGAP1 protein was elevated in skin fibroblasts obtained from patients with CSA, and it enhanced the PLC activity and peak intracellular calcium concentration in response to acetylcholine. IQGAP1, a novel stimulating protein, forms a complex with p122RhoGAP/DLC‐1 and PLC‐δ1 that moves along microtubules and enhances the PLC activity. |
| first_indexed | 2024-12-19T00:15:51Z |
| format | Article |
| id | doaj.art-c6b72d40f52f4f37a668a194fff431e0 |
| institution | Directory Open Access Journal |
| issn | 2573-9832 |
| language | English |
| last_indexed | 2024-12-19T00:15:51Z |
| publishDate | 2019-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | FASEB BioAdvances |
| spelling | doaj.art-c6b72d40f52f4f37a668a194fff431e02022-12-21T20:45:49ZengWileyFASEB BioAdvances2573-98322019-08-011846548010.1096/fba.2019-00020IQGAP1 activates PLC‐δ1 by direct binding and moving along microtubule with DLC‐1 to cell surfaceMakoto Tanaka0Tomohiro Osanai1Yoshimi Homma2Kenji Hanada3Ken Okumura4Hirofumi Tomita5Department of Stroke and Cerebrovascular Medicine Hirosaki University Graduate School of Medicine Hirosaki JapanDepartment of Nursing Science Hirosaki University Graduate School of Health Science Hirosaki JapanDepartment of Biomolecular Science Fukushima Medical University School of Medicine Fukushima JapanDepartment of Cardiology Hirosaki University Graduate School of Medicine Hirosaki JapanDivision of Cardiology Saiseikai Kumamoto Hospital Kumamoto JapanDepartment of Stroke and Cerebrovascular Medicine Hirosaki University Graduate School of Medicine Hirosaki JapanAbstract Phospholipase C (PLC)‐δ1, activated by p122RhoGTPase‐activating protein (GAP)/deleted in liver cancer‐1 (p122RhoGAP/DLC‐1), contributes to the coronary spastic angina (CSA) pathogenesis. The present study aims to further investigate the p122RhoGAP/DLC‐1 protein. We examined molecules assisting this protein and identified a scaffold protein—IQ motif‐containing GTPase‐activating protein 1 (IQGAP1). IQGAP1‐C binds to the steroidogenic acute regulatory‐related lipid transfer (START) domain of p122RhoGAP/DLC‐1, and PLC‐δ1 binds to IQGAP1‐N, forming a complex. In fluorescence microscopy, small dots of PLC‐δ1 created fine linear arrays like microtubules, and IQGAP1 and p122RhoGAP/DLC‐1 were colocated in the cytoplasm with PLC‐δ1. Ionomycin induced the raft recruitment of the PLC‐δ1, IQGAP1, and p122RhoGAP/DLC‐1 complex by translocation to the plasma membrane (PM), indicating the movement of this complex is along microtubules with the motor protein kinesin. Moreover, the IQGAP1 protein was elevated in skin fibroblasts obtained from patients with CSA, and it enhanced the PLC activity and peak intracellular calcium concentration in response to acetylcholine. IQGAP1, a novel stimulating protein, forms a complex with p122RhoGAP/DLC‐1 and PLC‐δ1 that moves along microtubules and enhances the PLC activity.https://doi.org/10.1096/fba.2019-00020acetylcholinecoronary spastic anginaIQ motif‐containing GTPase‐activating protein 1p122RhoGTPase‐activating protein (GAP)/deleted in liver cancer‐1phospholipase C |
| spellingShingle | Makoto Tanaka Tomohiro Osanai Yoshimi Homma Kenji Hanada Ken Okumura Hirofumi Tomita IQGAP1 activates PLC‐δ1 by direct binding and moving along microtubule with DLC‐1 to cell surface FASEB BioAdvances acetylcholine coronary spastic angina IQ motif‐containing GTPase‐activating protein 1 p122RhoGTPase‐activating protein (GAP)/deleted in liver cancer‐1 phospholipase C |
| title | IQGAP1 activates PLC‐δ1 by direct binding and moving along microtubule with DLC‐1 to cell surface |
| title_full | IQGAP1 activates PLC‐δ1 by direct binding and moving along microtubule with DLC‐1 to cell surface |
| title_fullStr | IQGAP1 activates PLC‐δ1 by direct binding and moving along microtubule with DLC‐1 to cell surface |
| title_full_unstemmed | IQGAP1 activates PLC‐δ1 by direct binding and moving along microtubule with DLC‐1 to cell surface |
| title_short | IQGAP1 activates PLC‐δ1 by direct binding and moving along microtubule with DLC‐1 to cell surface |
| title_sort | iqgap1 activates plc δ1 by direct binding and moving along microtubule with dlc 1 to cell surface |
| topic | acetylcholine coronary spastic angina IQ motif‐containing GTPase‐activating protein 1 p122RhoGTPase‐activating protein (GAP)/deleted in liver cancer‐1 phospholipase C |
| url | https://doi.org/10.1096/fba.2019-00020 |
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