IQGAP1: A Regulator of Intracellular Spacetime Relativity

Abstract

Activating and inhibiting receptors of lymphocytes collect valuable information about their mikròs kósmos. This information is essential to initiate or to turn off complex signaling pathways. Irrespective of these advances, our knowledge on how these intracellular activation cascades are coordinated in a spatiotemporal manner is far from complete. Amongst multiple explanations, the scaffolding proteins have emerged as a critical piece of this evolutionary tangram. Amongst many, IQGAP1 is one of the essential scaffolding proteins that coordinate multiple signaling pathways. IQGAP1 possesses multiple protein interaction motifs to achieve its scaffolding functions. Using these domains, IQGAP1 has been shown to regulate a number of essential cellular events. This includes actin polymerization, tubulin multimerization, MTOC formation, calcium/calmodulin signaling, Pak/Raf/Mek1/2-mediated Erk1/2 activation, formation of maestrosome, E-cadherin and CD44-mediated signaling and GSK3/APC-mediated β-catenin activation. In this review we summarize the recent developments and exciting new findings of cellular functions of IQGAP1.

Defective tubulin organization and proplatelet formation in murine megakaryocytes lacking Rac1 and Cdc42

“…Another recently emerging effector protein of Rac1 and Cdc42 is the scaffolding protein IQGAP1, which is implicated in the coordination of multiple cellular signaling processes leading to actin polymerization and tubulin multimerization in cell types other than platelets. 22 Intriguingly, IQGAP1 expression was significantly reduced in Rac1/Cdc42 2/2 MKs compared with in the wt MKs (P 5 .007). Together, these results indicate potential roles for cofilin and IQGAP1 in regulating actin and microtubule dynamics downstream of Rac1/Cdc42 during platelet production.…”

“…5 In contrast, actin-dependent mechanisms are thought to be involved in the branching of proplatelet shafts, thereby increasing the number of available proplatelet tips. 5 Rho GTPases are small proteins (20)(21)(22)(23)(24)(25) belonging to the superfamily of Ras-related proteins, which are found in all eukaryotic cells. 6 They are best known for regulating actin cytoskeletal dynamics in virtually all cell types, as well as for their involvement in the regulation of microtubules.…”

LIM kinase/cofilin dysregulation promotes macrothrombocytopenia in severe von Willebrand disease-type 2B

“…These unusually thick peripheral zones enriched in disorganized F-actin displayed an increased ratio of F-actin to globular actin (G-actin), indicating accumulation of actin polymerization ( Figure 4C and Supplemental Figure 7). Given the disorganization of the actin network, we considered the hypothesis that the activity of the actin turnover-regulating protein cofilin (8) or levels of the actin-binding scaffold protein IQGAP1 (25) could be modulated in 2B MKs. However, levels of IQGAP1 were similar in 2B and WT MKs ( Figure 5A).…”

IQGAP1 in Podosome /Invadosome is Involved in the Progression of Glioblastoma Multiforme Depending on the Tumor Status

“…Our study shows that an involvement of IQGAP1 in the spatiotemporal organization and activation of structural and signalling molecules [10,11] takes place not only in healthy cells, but in tumorigenic cells as well, specifically in GBM progression with different subcellular localizations and expression levels depending on the status of the cell within the tumor. Switching GBM to a successfully treatable entity will require a change from heterogeneous to a more homogeneous tumor status.…”

“…IQGAP1 connects elements of the cytoskeleton to cell adhesion and some signalling molecules and so modulates cell morphology, motility, cell cycle and other cellular functions [8,9] always facilitating and coordinating the spatiotemporal organization and the sequential activation of structural and signalling molecules [10,11]. As a result of this association with molecular partners, IQGAP1 contributes to cell fate, polarization, tumorigenesis, migration, tumour progression and angiogenesis [12,13].…”