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Colocalization of IQGAP1 with DLC-1 and PLC-δ1; Its potential role in coronary spasm

View ORCID ProfileMakoto Tanaka, Hirofumi Tomita, Kenji Hanada, View ORCID ProfileTomohiro Osanai, Yoshimi Homma, Ken Okumura
doi: https://doi.org/10.1101/526152
Makoto Tanaka
Hirosaki University;
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Hirofumi Tomita
Hirosaki University;
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Kenji Hanada
Hirosaki University;
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Tomohiro Osanai
Hirosaki University Graduate School of Health Science;
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Yoshimi Homma
Fukushima Medical University School;
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Ken Okumura
Saiseikai Kumamoto Hospital
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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.

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Posted January 23, 2019.
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Colocalization of IQGAP1 with DLC-1 and PLC-δ1; Its potential role in coronary spasm
Makoto Tanaka, Hirofumi Tomita, Kenji Hanada, Tomohiro Osanai, Yoshimi Homma, Ken Okumura
bioRxiv 526152; doi: https://doi.org/10.1101/526152
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Colocalization of IQGAP1 with DLC-1 and PLC-δ1; Its potential role in coronary spasm
Makoto Tanaka, Hirofumi Tomita, Kenji Hanada, Tomohiro Osanai, Yoshimi Homma, Ken Okumura
bioRxiv 526152; doi: https://doi.org/10.1101/526152

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