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

Makoto Tanaka1, Tomohiro Osanai2, Yoshimi Homma3

  • 1Department of Stroke and Cerebrovascular Medicine Hirosaki University Graduate School of Medicine Hirosaki Japan.

FASEB Bioadvances
|March 4, 2020
PubMed

Insights

IQGAP1 is a novel protein that forms a complex with p122RhoGAP/DLC-1 and Phospholipase C (PLC)-δ1. This complex moves along microtubules and enhances PLC activity, contributing to coronary spastic angina.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Cardiovascular Research

Background:

  • Phospholipase C (PLC)-δ1 activation by p122RhoGTPase-activating protein (GAP)/deleted in liver cancer-1 (p122RhoGAP/DLC-1) is implicated in coronary spastic angina (CSA) pathogenesis.
  • Further investigation into the p122RhoGAP/DLC-1 protein's interactions is warranted.

Purpose of the Study:

  • To identify and characterize proteins interacting with p122RhoGAP/DLC-1.
  • To elucidate the functional role of these interactions in cellular processes relevant to CSA.

Main Methods:

  • Protein-protein interaction analysis using co-localization studies and fluorescence microscopy.
  • Investigation of protein complex translocation along microtubules.
  • Assessment of IQGAP1 levels in patient-derived fibroblasts.
  • Enzyme activity assays for Phospholipase C (PLC).

Main Results:

  • IQ motif-containing GTPase-activating protein 1 (IQGAP1) was identified as a scaffold protein interacting with p122RhoGAP/DLC-1.
  • A ternary complex of PLC-δ1, IQGAP1, and p122RhoGAP/DLC-1 was characterized, with specific domain interactions noted (IQGAP1-C with p122RhoGAP/DLC-1 START domain, PLC-δ1 with IQGAP1-N).
  • The complex translocates along microtubules to the plasma membrane, involving kinesin motor proteins, and IQGAP1 levels are elevated in CSA patient fibroblasts, correlating with enhanced PLC activity and intracellular calcium.

Conclusions:

  • IQGAP1 is a novel stimulating protein that forms a functional complex with p122RhoGAP/DLC-1 and PLC-δ1.
  • This complex's microtubule-dependent movement and enhancement of PLC activity are significant findings.
  • Elevated IQGAP1 in CSA patients suggests its potential role in the disease's pathophysiology.
Keywords:
IQ motif‐containing GTPase‐activating protein 1acetylcholinecoronary spastic anginap122RhoGTPase‐activating protein (GAP)/deleted in liver cancer‐1phospholipase C

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