IQGAP1 activates PLC‐δ1 by direct binding and moving along microtubule with DLC‐1 to cell surface

• Published in: FASEB bioAdvances Vol. 1; no. 8; pp. 465 - 480
• Main Authors: Tanaka, Makoto, Osanai, Tomohiro, Homma, Yoshimi, Hanada, Kenji, Okumura, Ken, Tomita, Hirofumi
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.08.2019; John Wiley and Sons Inc; Wiley
• Subjects: Acetylcholine; Angina; Angina pectoris; Biotechnology; Calcium (intracellular); Cell surface; coronary spastic angina; Coronary vessels; Cytoplasm; Fibroblasts; Fluorescence microscopy; Guanosine triphosphatases; Ionomycin; IQ motif‐containing GTPase‐activating protein 1; IQGAP1 protein; Kinases; Kinesin; Liver cancer; Microscopy; Microtubules; p122RhoGTPase‐activating protein (GAP)/deleted in liver cancer‐1; Pathogenesis; Phospholipase C; Physiology; Plasmids; Proteins; Smooth muscle; Veins & arteries; United Kingdom > UK; United States > US; Japan; phospholipase C; p122RhoGTPase‐activating protein (GAP)/deleted in liver cancer‐1; IQ motif‐containing GTPase‐activating protein 1; acetylcholine; coronary spastic angina
• ISSN: 2573-9832; 2573-9832
• DOI: 10.1096/fba.2019-00020

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.