IQGAP1 and its binding proteins control diverse biological functions

Abstract

IQGAP proteins have been identified in a wide spectrum of organisms, ranging from yeast to humans. The most extensively studied family member is the ubiquitously expressed scaffold protein IQGAP1, which participates in multiple essential aspects of mammalian biology. IQGAP1 mediates these effects by binding to and regulating the function of numerous interacting proteins. Over ninety proteins have been reported to associate with IQGAP1, either directly or as part of a larger complex. In this review, we summarise those IQGAP1 binding partners that have been identified in the last five years. The molecular mechanisms by which these interactions contribute to the functions of receptors and their signalling cascades, small GTPase function, cytoskeletal dynamics, neuronal regulation and intracellular trafficking are evaluated. The evidence that has accumulated recently validates the role of IQGAP1 as a scaffold protein and expands the repertoire of cellular activities in which it participates.

RSPO–LGR4 functions via IQGAP1 to potentiate Wnt signaling

“…This pathway regulates cell polarity and migration through modulating activities of the Rho family of GTPases (Rho, Rac, and CDC42), which all interact with IQGAPs directly (35,36,42). Importantly, IQGAP1 can recruit the actin assembly proteins neural Wiskott-Aldrich syndrome protein (N-WASP) and mDia1 to coordinate receptor activation with FA assembly, which is critical to the control of cell adhesion and migration (43)(44)(45).…”

“…Of the many putative proteins identified (Table S1), two candidates, IQGAP1 and IQGAP3, were particularly notable for their pleiotropic roles in signal transduction (35,36). The three highly homologous IQGAPs (IQGAP1-3) contain multiple domains that bind to and modulate the activity of a plethora of signaling molecules, including Rho GTPases, MAP kinase (MAPK), and components of Wnt pathway E-cadherin, β-catenin, and adenomatous polyposis coli (35,36). We first confirmed that full-length LGR4 interacts with IQGAP1 as well as with IQGAP2 and IQGAP3 by co-IP analysis ( Fig.…”

“…IQGAPs contain several domains that bind to distinct signaling and structural proteins (35,36). To map the IQGAP1 domain responsible for interacting with LGR4, a series of IQGAP1 truncation and deletion mutants were constructed (Fig.…”

G-protein–coupled receptor GPR161 is overexpressed in breast cancer and is a promoter of cell proliferation and invasion

“…To define the mechanism by which GPR161 induces proliferation, migration, and invasion, we focused on an adherens junction-localized scaffold protein that is related to GPCR signaling. IQGAP1 regulates a vast array of cellular functions through interactions with proteins such as E-cad, Neural Wiskott-Aldrich syndrome protein (N-WASP), Cdc42, and the exocyst complex (19). IQGAP1 has been reported to interact with βArr2, a scaffold protein that binds to activated GPCRs and regulates signaling and receptor endocytosis (20).…”

Hepatocyte Growth Factor-induced Asef-IQGAP1 Complex Controls Cytoskeletal Remodeling and Endothelial Barrier

“…IQGAP1 is a multifunctional adaptor protein involved in the coordination of diverse cellular processes, including receptor activation, regulation of MAPK signaling, activity of small GTPases, the regulation of cytoskeletal remodeling, and assembly of cell junctions (23)(24)(25)(26). IQGAP1 controls microtubule and actin cytoskeletal dynamics via interactions with small GTPases Rac1 and Cdc42.…”