IQGAP1: Insights into the function of a molecular puppeteer

• Scaffolins play an essential role in coordinating signaling events in cells.
• As a scaffolin, IQGAP1 curbs, compartmentalizes, and coordinates signaling events.
• IQGAP1 connects extracellular signals to the genome to elicit functional responses.
• Spatiotemporal organization of signaling events coordinated by IQGAP1.
• IQGAP1 regulates cytoskeleton, MAPK pathway, and β-catenin activation.

The intracellular spatiotemporal organization of signaling events is critical for normal cellular function. In response to environmental stimuli, cells utilize highly organized signaling pathways that are subject to multiple layers of regulation. However, the molecular mechanisms that coordinate these complex processes remain an enigma. Scaffolding proteins (scaffolins) have emerged as critical regulators of signaling pathways, many of which have well-described functions in immune cells. IQGAP1, a highly conserved cytoplasmic scaffold protein, is able to curb, compartmentalize, and coordinate multiple signaling pathways in a variety of cell types. IQGAP1 plays a central role in cell–cell interaction, cell adherence, and movement via actin/tubulin-based cytoskeletal reorganization. Evidence also implicates IQGAP1 as an essential regulator of the MAPK and Wnt/β-catenin signaling pathways. Here, we summarize the recent advances on the cellular and molecular biology of IQGAP1. We also describe how this pleiotropic scaffolin acts as a true molecular puppeteer, and highlight the significance of future research regarding the role of IQGAP1 in immune cells.